Skip Navigation
Skip to contents

Cancer Res Treat : Cancer Research and Treatment

OPEN ACCESS

Search

Page Path
HOME > Search
36 "Tae-You Kim"
Filter
Filter
Article category
Keywords
Publication year
Authors
Funded articles
Original Articles
Breast cancer
Harnessing Institutionally Developed Clinical Targeted Sequencing to Improve Patient Survival in Breast Cancer: A Seven-Year Experience
Jiwon Koh, Jinyong Kim, Go-Un Woo, Hanbaek Yi, So Yean Kwon, Jeongmin Seo, Jeong Mo Bae, Jung Ho Kim, Jae Kyung Won, Han Suk Ryu, Yoon Kyung Jeon, Dae-Won Lee, Miso Kim, Tae-Yong Kim, Kyung-Hun Lee, Tae-You Kim, Jee-Soo Lee, Moon-Woo Seong, Sheehyun Kim, Sungyoung Lee, Hongseok Yun, Myung Geun Song, Jaeyong Choi, Jong-Il Kim, Seock-Ah Im
Cancer Res Treat. 2025;57(2):443-456.   Published online August 21, 2024
DOI: https://doi.org/10.4143/crt.2024.296
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world.
Materials and Methods
We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis.
Results
NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs.
Conclusion
Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.
  • 1,540 View
  • 149 Download
Close layer
Lung and Thoracic cancer
Analytical and Clinical Validation of a Highly Sensitive NGS-Based ctDNA Assay with Real-World Concordance in Non–Small Cell Lung Cancer
Hanbaek Yi, Jeonghwan Youk, Yoojoo Lim, Hanseong Roh, Dongsoo Kyung, Hwang-Phill Kim, Duhee Bang, Bhumsuk Keam, Tae-Min Kim, Miso Kim, Dong-Wan Kim, Tae-You Kim
Cancer Res Treat. 2024;56(3):765-773.   Published online January 8, 2024
DOI: https://doi.org/10.4143/crt.2023.1294
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
There have been needs to improve the sensitivity of liquid biopsy. This report aims to report the analytical and clinical validation of a next-generation sequencing (NGS)–based circulating tumor DNA (ctDNA) assay.
Materials and Methods
Analytical validation was conducted in vitro by evaluating the limit of detection (LOD), precision, and specificity for various genomic aberrations. The real-world performance in non–small cell lung cancer (NSCLC) was assessed by comparing the results of AlphaLiquid100 to the tissue-based results.
Results
The LODs with 30 ng input DNA were 0.11%, 0.11%, 0.06%, 0.21%, and 2.13 copies for detecting single nucleotide variants, insertions, deletions, fusions, and copy number alterations (CNA), respectively. Quantitatively, single nucleotide variants/insertions and deletions, fusions, and CNAs showed a good correlation (R2=0.91, 0.40, and 0.65; y=0.95, 1.06, and 1.19) to the manufacturer’s values, and per-base specificities for all types of variants were near 100%. In real-world NSCLC (n=122), key actionable mutations in NSCLC were detected in 60.7% (74/122) with the ctDNA assay. Comparative analysis against the NGS-based tissue results for all key mutations showed positive percent agreement (PPA) of 85.3%. For individual genes, the PPA was as high as 95.7% for epidermal growth factor receptor (EGFR) mutations and 83.3% for ALK translocations. AlphaLiquid100 detected drug-sensitive EGFR mutation at a variant allele frequency as low as 0.02% and also identified an EGFR mutation in a case where tissue sample missed. Blood samples collected post-targeted therapies revealed additional acquired mutations.
Conclusion
The AlphaLiquid100 ctDNA assay demonstrates robust analytical validity, offering clinically important information for NSCLC patients.

Citations

Citations to this article as recorded by  
  • Reporting of molecular test results from cell-free DNA analyses: expert consensus recommendations from the 2023 European Liquid Biopsy Society ctDNA Workshop
    Vincent D. de Jager, Patrizio Giacomini, Jennifer A. Fairley, Rodrigo A. Toledo, Simon J. Patton, Simon A. Joosse, Claudia Koch, Zandra C. Deans, Sofia Agelaki, Claus Lindbjerg Andersen, Daniel Andersson, Beatriz Bellosillo, Inger Riise Bergheim, Daan van
    eBioMedicine.2025; 114: 105636.     CrossRef
  • Next-generation sequencing impact on cancer care: applications, challenges, and future directions
    Mariano Zalis, Gilson Gabriel Viana Veloso, Pedro Nazareth Aguiar Jr., Nathalia Gimenes, Marina Xavier Reis, Silvio Matsas, Carlos Gil Ferreira
    Frontiers in Genetics.2024;[Epub]     CrossRef
  • Profiling Cell-Free DNA from Malignant Pleural Effusion for Oncogenic Driver Mutations in Patients with Treatment-Naive Stage IV Adenocarcinoma: A Multicenter Prospective Study
    Shih-Chieh Chang, Yu-Feng Wei, Chung-Yu Chen, Yi-Chun Lai, Po-Wei Hu, Jui-Chi Hung, Cheng-Yu Chang
    Molecular Diagnosis & Therapy.2024; 28(6): 803.     CrossRef
  • Concordance of ctDNA and tissue genomic profiling in advanced biliary tract cancer
    Sohyun Hwang, Seonjeong Woo, Beodeul Kang, Haeyoun Kang, Jung Sun Kim, Sung Hwan Lee, Chang Il Kwon, Dong Soo Kyung, Hwang-Phill Kim, Gwangil Kim, Chan Kim, Hong Jae Chon
    Journal of Hepatology.2024;[Epub]     CrossRef
  • 6,146 View
  • 377 Download
  • 3 Web of Science
  • 4 Crossref
Close layer
Gastrointestinal cancer
A Phase 1b/2a Study of GC1118 with 5-Fluorouracil, Leucovorin and Irinotecan (FOLFIRI) in Patients with Recurrent or Metastatic Colorectal Cancer
Keun-Wook Lee, Sae-Won Han, Tae Won Kim, Joong Bae Ahn, Ji Yeon Baek, Sang Hee Cho, Howard Lee, Jin Won Kim, Ji-Won Kim, Tae-You Kim, Yong Sang Hong, Seung-Hoon Beom, Yongjun Cha, Yoonjung Choi, Seonhui Kim, Yung-Jue Bang
Cancer Res Treat. 2024;56(2):590-601.   Published online December 7, 2023
DOI: https://doi.org/10.4143/crt.2023.1117
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
GC1118 is a novel antibody targeting epidermal growth factor receptor (EGFR) with enhanced blocking activity against both low- and high-affinity EGFR ligands. A phase 1b/2a study was conducted to determine a recommended phase 2 dose (RP2D) of GC1118 in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) (phase 1b) and to assess the safety and efficacy of GC1118 plus FOLFIRI as a second-line therapy for recurrent/metastatic colorectal cancer (CRC) (phase 2a).
Materials and Methods
Phase 1b was designed as a standard 3+3 dose-escalation study with a starting dose of GC1118 (3 mg/kg/week) in combination with biweekly FOLFIRI (irinotecan 180 mg/m2; leucovorin 400 mg/m2; 5-fluorouracil 400 mg/m2 bolus and 2,400 mg/m2 infusion over 46 hours) in patients with solid tumors refractory to standard treatments. The subsequent phase 2a part was conducted with objective response rate (ORR) as a primary endpoint. Patients with KRAS/NRAS/BRAF wild-type, EGFR-positive, recurrent/metastatic CRC resistant to the first-line treatment were enrolled in the phase 2a study.
Results
RP2D of GC1118 was determined to be 3 mg/kg/wk in the phase 1b study (n=7). Common adverse drug reactions (ADRs) observed in the phase 2a study (n=24) were acneiform rash (95.8%), dry skin (66.7%), paronychia (58.3%), and stomatitis (50.0%). The most common ADR of ≥ grade 3 was neutropenia (33.3%). ORR was 42.5% (95% confidence interval [CI], 23.5 to 62.0), and median progression-free survival was 6.7 months (95% CI, 4.0-8.0).
Conclusion
GC1118 administered weekly at 3 mg/kg in combination with FOLFIRI appears as an effective and safe treatment option in recurrent/metastatic CRC.

Citations

Citations to this article as recorded by  
  • Drug combinations of camptothecin derivatives promote the antitumor properties
    Zhen Liu, Yajie Yuan, Ning Wang, Peng Yu, Yuou Teng
    European Journal of Medicinal Chemistry.2024; 279: 116872.     CrossRef
  • 3,839 View
  • 141 Download
  • 1 Web of Science
  • 1 Crossref
Close layer
Circulating Tumor DNA Dynamics and Treatment Outcome of Regorafenib in Metastatic Colorectal Cancer
Dae-Won Lee, Yoojoo Lim, Hwang-Phill Kim, Su Yeon Kim, Hanseong Roh, Jun-Kyu Kang, Kyung‑Hun Lee, Min Jung Kim, Seung-Bum Ryoo, Ji Won Park, Seung-Yong Jeong, Kyu Joo Park, Gyeong Hoon Kang, Sae-Won Han, Tae-You Kim
Cancer Res Treat. 2023;55(3):927-938.   Published online March 7, 2023
DOI: https://doi.org/10.4143/crt.2023.268
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Circulating tumor DNA (ctDNA) is emerging as a valuable non-invasive tool to identify tumor heterogeneity and tumor burden. This study investigated ctDNA dynamics in metastatic colorectal cancer patients treated with regorafenib.
Materials and Methods
In this prospective biomarker study, plasma cell-free DNA (cfDNA) samples obtained at baseline, at the first response evaluation after 2 cycles of treatment, and at the time of progressive disease were sequenced using a targeted next-generation sequencing platform which included 106 genes.
Results
A total of 285 blood samples from 110 patients were analyzed. Higher baseline cfDNA concentration was associated with worse progression-free survival (PFS) and overall survival (OS). After 2 cycles of treatment, variant allele frequency (VAF) in the majority of ctDNA mutations decreased with a mean relative change of –31.6%. Decreases in the VAF of TP53, APC, TCF7L2, and ROS1 after 2 cycles of regorafenib were associated with longer PFS. We used the sum of VAF at each time point as a surrogate for the overall ctDNA burden. A reduction in sum (VAF) of ≥ 50% after 2 cycles was associated with longer PFS (6.1 vs. 2.7 months, p=0.002), OS (11.3 vs. 5.9 months, p=0.001), and higher disease control rate (86.3% vs. 51.1%, p < 0.001). VAF of the majority of the ctDNA mutations increased at the time of disease progression, and VAF of BRAF increased markedly.
Conclusion
Reduction in ctDNA burden as estimated by sum (VAF) could be used to predict treatment outcome of regorafenib.

Citations

Citations to this article as recorded by  
  • A Systematic Review and Meta-Analysis of the Efficacy and Safety of Regorafenib in the Treatment of Metastatic Colorectal Cancer
    Bingjun Liang, Ming Tang, Chao Huang, Yidian Yang, Yue He, Shengrong Liao, Weizeng Shen
    Journal of Gastrointestinal Cancer.2025;[Epub]     CrossRef
  • Pairwise analysis of plasma cell-free DNA before and after palliative second-line paclitaxel plus ramucirumab treatment in patients with metastatic gastric cancer
    Ji-Won Kim, Dong Soo Kyung, Won Yeong Ko, Hwang-Phill Kim, Sung-Hyun Hwang, Kui-Jin Kim, Ju Hyun Lee, Jeongmin Seo, Minsu Kang, Eun Hee Jung, Koung Jin Suh, Se Hyun Kim, Jin Won Kim, Yu Jung Kim, Jee Hyun Kim, Keun-Wook Lee
    Gastric Cancer.2025;[Epub]     CrossRef
  • Adjuvant therapy for stage IIB + IIC melanoma
    Parisa Malekzadeh, Mary S. Brady
    Journal of Surgical Oncology.2024; 129(1): 91.     CrossRef
  • Variant allele frequency in circulating tumor DNA correlated with tumor disease burden and predicted outcomes in patients with advanced breast cancer
    Jianxin Zhong, Hanfang Jiang, Xiaoran Liu, Hao Liao, Feng Xie, Bin Shao, Shidong Jia, Huiping Li
    Breast Cancer Research and Treatment.2024; 204(3): 617.     CrossRef
  • Stage-Specific Plasma Metabolomic Profiles in Colorectal Cancer
    Tetsuo Ishizaki, Masahiro Sugimoto, Yu Kuboyama, Junichi Mazaki, Kenta Kasahara, Tomoya Tago, Ryutaro Udo, Kenichi Iwasaki, Yutaka Hayashi, Yuichi Nagakawa
    Journal of Clinical Medicine.2024; 13(17): 5202.     CrossRef
  • Nivolumab plus anlotinib hydrochloride in advanced gastric adenocarcinoma and esophageal squamous cell carcinoma: the phase II OASIS trial
    Jing Wu, Shilong Zhang, Shan Yu, Guo An, Yi Wang, Yiyi Yu, Li Liang, Yan Wang, Xiaojing Xu, YanShi Xiong, Di Shao, Zhun Shi, Nannan Li, Jingyuan Wang, Dawei Jin, Tianshu Liu, Yuehong Cui
    Nature Communications.2024;[Epub]     CrossRef
  • The Diagnostic Utility of cfDNA and ctDNA in Liquid Biopsies for Gastrointestinal Cancers over the Last Decade
    Nur Rahadiani, Marini Stephanie, Amelia Fossetta Manatar, Ening Krisnuhoni
    Oncology Research and Treatment.2024; 48(3): 125.     CrossRef
  • Mutational evolution after chemotherapy‐progression in metastatic colorectal cancer revealed by circulating tumor DNA analysis
    Sheehyun Kim, Yongjun Cha, Yoojoo Lim, Hanseong Roh, Jun‐Kyu Kang, Kyung‐Hun Lee, Min Jung Kim, Ji Won Park, Seung‐Bum Ryoo, Hwang‐Phill Kim, Seung‐Yong Jeong, Kyu Joo Park, Sae‐Won Han, Tae‐You Kim
    International Journal of Cancer.2023; 153(3): 571.     CrossRef
  • A Phase II Exploratory Study to Identify Biomarkers Predictive of Clinical Response to Regorafenib in Patients with Metastatic Colorectal Cancer Who Have Failed First-Line Therapy
    Karen Gambaro, Maud Marques, Suzan McNamara, Mathilde Couetoux du Tertre, Cyrla Hoffert, Archana Srivastava, Anna Schab, Thierry Alcindor, Adrian Langleben, Lucas Sideris, Mahmoud Abdelsalam, Mustapha Tehfe, Felix Couture, Gerald Batist, Petr Kavan
    International Journal of Molecular Sciences.2023; 25(1): 43.     CrossRef
  • 5,590 View
  • 271 Download
  • 9 Web of Science
  • 9 Crossref
Close layer
Case Report
Efficacy of Olaparib in Treatment-Refractory, Metastatic Breast Cancer with Uncommon Somatic BRCA Mutations Detected in Circulating Tumor DNA
Jung-Ki Yoon, Jongseong Ahn, Sheehyun Kim, Hwang-Phil Kim, Jun-kyu Kang, Duhee Bang, Yoojoo Lim, Tae-You Kim
Cancer Res Treat. 2023;55(3):1048-1052.   Published online January 31, 2023
DOI: https://doi.org/10.4143/crt.2022.1529
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Poly(ADP-ribose) polymerase inhibitors have been shown dramatic responses in patients with BRCAness. However, clinical studies have been limited to breast cancer patients with germline mutations. Here, we describe a patient with metastatic breast cancer who had a rare BRCA1 somatic mutation (BRCA1 c.4336G>T (p.E1446*)) detected by cell-free DNA analysis after failing standard therapies. This tier III variant of unknown significance was predicted to be a pathogenic variant in our assessment, leading us to consider off-label treatment with olaparib. The patient responded well to olaparib for several months, with a decrease in allele frequency of this BRCA1 somatic mutation in cell-free DNA. Olaparib resistance subsequently developed with an increase in the allele frequency and new BRCA1 reversion mutations. To our knowledge, this is the first report confirming BRCA1 c.4336G>T (p.E1446*) as a mutation sensitive to olaparib in breast cancer and describing the dynamic changes in the associated mutations using liquid biopsy.

Citations

Citations to this article as recorded by  
  • Circulating tumor DNA validity and potential uses in metastatic breast cancer
    Ottavia Amato, Nefeli Giannopoulou, Michail Ignatiadis
    npj Breast Cancer.2024;[Epub]     CrossRef
  • DNA damage targeted therapy for advanced breast cancer
    Vanessa Patel, Sandra Casimiro, Catarina Abreu, Tiago Barroso, Rita Teixeira de Sousa, Sofia Torres, Leonor Abreu Ribeiro, Gonçalo Nogueira-Costa, Helena Luna Pais, Conceição Pinto, Leila Costa, Luís Costa
    Exploration of Targeted Anti-tumor Therapy.2024; 5(3): 678.     CrossRef
  • Practical Utility of Liquid Biopsies for Evaluating Genomic Alterations in Castration-Resistant Prostate Cancer
    Seung-Hwan Jeong, Dongsoo Kyung, Hyeong Dong Yuk, Chang Wook Jeong, Wookjae Lee, Jung-Ki Yoon, Hwang-Phill Kim, Duhee Bang, Tae-You Kim, Yoojoo Lim, Cheol Kwak
    Cancers.2023; 15(10): 2847.     CrossRef
  • 4,602 View
  • 266 Download
  • 2 Web of Science
  • 3 Crossref
Close layer
Original Articles
General
Radiation Response Prediction Model Based on Integrated Clinical and Genomic Data Analysis
Bum-Sup Jang, Ji-Hyun Chang, Seung Hyuck Jeon, Myung Geun Song, Kyung-Hun Lee, Seock-Ah Im, Jong-Il Kim, Tae-You Kim, Eui Kyu Chie
Cancer Res Treat. 2022;54(2):383-395.   Published online August 24, 2021
DOI: https://doi.org/10.4143/crt.2021.759
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The value of the genomic profiling by targeted gene-sequencing on radiation therapy response prediction was evaluated through integrated analysis including clinical information. Radiation response prediction model was constructed based on the analyzed findings.
Materials and Methods
Patients who had the tumor sequenced using institutional cancer panel after informed consent and received radiotherapy for the measurable disease served as the target cohort. Patients with irradiated tumor locally controlled for more than 6 months after radiotherapy were defined as the durable local control (DLC) group, otherwise, non-durable local control (NDLC) group. Significant genomic factors and domain knowledge were used to develop the Bayesian Network model to predict radiotherapy response.
Results
Altogether, 88 patients were collected for analysis. Of those, 41 (43.6%) and 47 (54.4%) patients were classified as the NDLC and DLC group, respectively. Somatic mutations of NOTCH2 and BCL were enriched in the NDLC group, whereas, mutations of CHEK2, MSH2, and NOTCH1 were more frequently found in the DLC group. Altered DNA repair pathway was associated with better local failure–free survival (hazard ratio, 0.40; 95% confidence interval, 0.19 to 0.86; p=0.014). Smoking somatic signature was found more frequently in the DLC group. Area under the receiver operating characteristic curve of the Bayesian network model predicting probability of 6-month local control was 0.83.
Conclusion
Durable radiation response was associated with alterations of DNA repair pathway and smoking somatic signature. Bayesian network model could provide helpful insights for high precision radiotherapy. However, these findings should be verified in prospective cohort for further individualization.

Citations

Citations to this article as recorded by  
  • Estimating the risk and benefit of radiation therapy in (y)pN1 stage breast cancer patients: A Bayesian network model incorporating expert knowledge (KROG 22–13)
    Bum-Sup Jang, Seok-Joo Chun, Hyeon Seok Choi, Ji Hyun Chang, Kyung Hwan Shin
    Computer Methods and Programs in Biomedicine.2024; 245: 108049.     CrossRef
  • Prediction of Overall Disease Burden in (y)pN1 Breast Cancer Using Knowledge-Based Machine Learning Model
    Seok-Joo Chun, Bum-Sup Jang, Hyeon Seok Choi, Ji Hyun Chang, Kyung Hwan Shin
    Cancers.2024; 16(8): 1494.     CrossRef
  • Selection of patients with pancreatic adenocarcinoma who may benefit from radiotherapy
    I-Shiow Jan, Hui Ju Ch’ang
    Radiation Oncology.2023;[Epub]     CrossRef
  • Characterization of the gene signature correlated with favorable response to chemoradiotherapy in rectal cancer: A hypothesis‐generating study
    Seung Hyuck Jeon, Eui Kyu Chie
    Cancer Medicine.2023; 12(7): 8981.     CrossRef
  • Krüppel-like Factor 10 as a Prognostic and Predictive Biomarker of Radiotherapy in Pancreatic Adenocarcinoma
    Yi-Chih Tsai, Min-Chieh Hsin, Rui-Jun Liu, Ting-Wei Li, Hui-Ju Ch’ang
    Cancers.2023; 15(21): 5212.     CrossRef
  • 6,120 View
  • 183 Download
  • 5 Web of Science
  • 5 Crossref
Close layer
Gastrointestinal Cancer
Phase II Trial of Postoperative Adjuvant Gemcitabine and Cisplatin Chemotherapy Followed by Chemoradiotherapy with Gemcitabine in Patients with Resected Pancreatic Cancer
Kyung-Hun Lee, Eui Kyu Chie, Seock-Ah Im, Jee Hyun Kim, Jihyun Kwon, Sae-Won Han, Do-Youn Oh, Jin-Young Jang, Jae-Sung Kim, Tae-You Kim, Yung-Jue Bang, Sun Whe Kim, Sung W. Ha
Cancer Res Treat. 2021;53(4):1096-1103.   Published online December 30, 2020
DOI: https://doi.org/10.4143/crt.2020.928
AbstractAbstract PDFPubReaderePub
Purpose
Despite curative resection, the 5-year survival for patients with resectable pancreatic cancer is less than 20%. Recurrence occurs both locally and at distant sites and effective multimodality adjuvant treatment is needed.
Materials and Methods
Patients with curatively resected stage IB-IIB pancreatic adenocarcinoma were eligible. Treatment consisted of chemotherapy with gemcitabine 1,000 mg/m2 on days 1 and 8 and cisplatin 60 mg/m2 on day 1 every 3 weeks for two cycles, followed by chemoradiotherapy (50.4 Gy/28 fx) with weekly gemcitabine (300 mg/m2/wk), and then gemcitabine 1,000 mg/m2 on days 1 and 8 every 3 weeks for four cycles. The primary endpoint was 1-year disease-free survival rate. The secondary endpoints were disease-free survival, overall survival, and safety.
Results
Seventy-four patients were enrolled. One-year disease-free survival rate was 57.9%. Median disease-free and overall survival were 15.0 months (95% confidence interval [CI], 11.6 to 18.4) and 33.0 months (95% CI, 21.8 to 44.2), respectively. At the median follow-up of 32 months, 57 patients (77.0%) had recurrence including 11 patients whose recurrence was during the adjuvant treatment. Most of the recurrences were systemic (52 patients). Stage at the time of diagnosis (70.0% in IIA, 51.2% in IIB, p=0.006) were significantly related with 1-year disease-free survival rate. Toxicities were generally tolerable, with 53 events of grade 3 or 4 hematologic toxicity and four patients with febrile neutropenia.
Conclusion
Adjuvant gemcitabine and cisplatin chemotherapy followed by chemoradiotherapy with gemcitabine and maintenance gemcitabine showed efficacy and good tolerability in curatively resected pancreatic cancer.

Citations

Citations to this article as recorded by  
  • NUDT21 interacts with NDUFS2 to activate the PI3K/AKT pathway and promotes pancreatic cancer pathogenesis
    Xiao-Dong Huang, Yong-Wei Chen, Lv Tian, Li Du, Xiao-Chen Cheng, Yu-Xin Lu, Dong-Dong Lin, Feng-Jun Xiao
    Journal of Cancer Research and Clinical Oncology.2024;[Epub]     CrossRef
  • Efficacy of Cisplatin-Containing Chemotherapy Regimens in Patients of Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-analysis
    Obaid Ur Rehman, Eeshal Fatima, Zain Ali Nadeem, Arish Azeem, Jatin Motwani, Habiba Imran, Hadia Mehboob, Alishba Khan, Omer Usman
    Journal of Gastrointestinal Cancer.2024; 55(2): 559.     CrossRef
  • OTUB1/NDUFS2 axis promotes pancreatic tumorigenesis through protecting against mitochondrial cell death
    Xiao-Dong Huang, Li Du, Xiao-Chen Cheng, Yu-Xin Lu, Qiao-Wei Liu, Yi-Wu Wang, Ya-Jin Liao, Dong-Dong Lin, Feng-Jun Xiao
    Cell Death Discovery.2024;[Epub]     CrossRef
  • Impact of obesity on pathological complete remission in early stage breast cancer patients after neoadjuvant chemotherapy: a retrospective study from a German University breast center
    Johannes Felix Englisch, Alexander Englisch, Dominik Dannehl, Kenneth Eissler, Christian Martin Tegeler, Sabine Matovina, Léa Louise Volmer, Diethelm Wallwiener, Sara Y. Brucker, Andreas Hartkopf, Tobias Engler
    Archives of Gynecology and Obstetrics.2024; 311(2): 437.     CrossRef
  • A Photothermal Therapy Study Based on Electrospinning Nanofibers Blended and Coated with Polydopamine Nanoparticles
    Chunhong Sui, Yijia Luo, Xiao Xiao, Jiaxue Liu, Xiaotong Shao, Yingxue Xue, Cheng Wang, Wenliang Li
    ChemistrySelect.2023;[Epub]     CrossRef
  • Ivermectin and gemcitabine combination treatment induces apoptosis of pancreatic cancer cells via mitochondrial dysfunction
    Da Eun Lee, Hyeon Woong Kang, So Yi Kim, Myeong Jin Kim, Jae Woong Jeong, Woosol Chris Hong, Sungsoon Fang, Hyung Sun Kim, Yun Sun Lee, Hyo Jung Kim, Joon Seong Park
    Frontiers in Pharmacology.2022;[Epub]     CrossRef
  • CircLMTK2 Silencing Attenuates Gemcitabine Resistance in Pancreatic Cancer by Sponging miR-485-5p and to Target PAK1
    Yeting Lu, Shuping Zhou, Gong Cheng, Yi Ruan, Yuan Tian, Kaiji Lv, Shuo Han, Xinhua Zhou, Xiangya Ding
    Journal of Oncology.2022; 2022: 1.     CrossRef
  • Effects of Radiotherapy and Chemotherapy on Postoperative Prognosis of Patients Undergoing Radical Surgery for Pancreatic Cancer—Based on SEER Database Analysis
    媛媛 苏
    Advances in Clinical Medicine.2022; 12(10): 9540.     CrossRef
  • Zebrafish Patient-Derived Xenografts Identify Chemo-Response in Pancreatic Ductal Adenocarcinoma Patients
    Alice Usai, Gregorio Di Franco, Margherita Piccardi, Perla Cateni, Luca Emanuele Pollina, Caterina Vivaldi, Enrico Vasile, Niccola Funel, Matteo Palmeri, Luciana Dente, Alfredo Falcone, Dimitri Giunchi, Alessandro Massolo, Vittoria Raffa, Luca Morelli
    Cancers.2021; 13(16): 4131.     CrossRef
  • Hypoxia-Induced ZWINT Mediates Pancreatic Cancer Proliferation by Interacting With p53/p21
    Peng Chen, Zhiwei He, Jie Wang, Jian Xu, Xueyi Jiang, Yankun Chen, Xinyuan Liu, Jianxin Jiang
    Frontiers in Cell and Developmental Biology.2021;[Epub]     CrossRef
  • 7,312 View
  • 153 Download
  • 10 Crossref
Close layer
Gastrointestinal cancer
A Phase II Study of Avelumab Monotherapy in Patients with Mismatch Repair–Deficient/Microsatellite Instability–High or POLE-Mutated Metastatic or Unresectable Colorectal Cancer
Jwa Hoon Kim, Sun Young Kim, Ji Yeon Baek, Yong Jun Cha, Joong Bae Ahn, Han Sang Kim, Keun-Wook Lee, Ji-Won Kim, Tae-You Kim, Won Jin Chang, Joon Oh Park, Jihun Kim, Jeong Eun Kim, Yong Sang Hong, Yeul Hong Kim, Tae Won Kim
Cancer Res Treat. 2020;52(4):1135-1144.   Published online April 24, 2020
DOI: https://doi.org/10.4143/crt.2020.218
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
We evaluated the efficacy and safety of avelumab, an anti-PD-L1 antibody, in patients with metastatic or unresectable colorectal cancer (mCRC) with mismatch repair deficiency (dMMR)/microsatellite instability-high (MSI-H) or POLE mutations.
Materials and Methods
In this prospective, open-label, multicenter phase II study, 33 patients with mCRC harboring dMMR/MSI-H or POLE mutations after failure of ≥1st-line chemotherapy received avelumab 10 mg/kg every 2 weeks. dMMR/MSI-H was confirmed with immunohistochemical staining (IHC) by loss of expression of MMR proteins or polymerase chain reaction (PCR) for microsatellite sequences. POLE mutation was confirmed by next-generation sequencing (NGS). The primary endpoint was the objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors ver. 1.1.
Results
The median age was 60 years, and 78.8% were male. Thirty patients were dMMR/MSI-H and three had POLE mutations. The ORR was 24.2%, and all of the responders were dMMR/MSI-H. For 21 patients with MSI-H by PCR or NGS, the ORR was 28.6%. At a median follow-up duration of 16.3 months, median progression-free survival and overall survival were 3.9 and 13.2 months in all patients, and 8.1 months and not reached, respectively, in patients with MSI-H by PCR or NGS. Dose interruption and discontinuation due to treatment-related adverse events occurred in 4 and 2 patients, respectively, with no treatment-related deaths.
Conclusion
Avelumab displayed antitumor activity with manageable toxicity in patients with previously treated mCRC harboring dMMR/MSI-H. Diagnosis of dMMR/MSI-H with PCR or NGS could be complementary to IHC to select patients who would benefit from immunotherapy.

Citations

Citations to this article as recorded by  
  • Current efficacy of immune checkpoint inhibitors in microsatellite unstable colorectal cancer and potential biomarkers
    Mariam Rojas, Clara Rodrigo, Reinaldo Moreno, Marta Cascante, Joan Maurel
    Exploration of Digestive Diseases.2025;[Epub]     CrossRef
  • Optimal early endpoint for second-line or subsequent immune checkpoint inhibitors in previously treated advanced solid cancers: a systematic review
    Jingqiu Li, Xiaoding Zhou, Lei Wu, Jiabao Ma, Yan Tan, Songke Wu, Jie Zhu, Qifeng Wang, Qiuling Shi
    BMC Cancer.2025;[Epub]     CrossRef
  • Molecular subtypes of endometrial cancer: Implications for adjuvant treatment strategies
    Ye Yang, Su Fang Wu, Wei Bao
    International Journal of Gynecology & Obstetrics.2024; 164(2): 436.     CrossRef
  • Immune checkpoint inhibitors in colorectal cancer: limitation and challenges
    Suying Yan, Wanting Wang, Zhiqiang Feng, Jun Xue, Weizheng Liang, Xueliang Wu, Zhiquan Tan, Xipeng Zhang, Shuai Zhang, Xichuan Li, Chunze Zhang
    Frontiers in Immunology.2024;[Epub]     CrossRef
  • Navigating through novelties concerning mCRC treatment—the role of immunotherapy, chemotherapy, and targeted therapy in mCRC
    Edward Zheng, Marcin Włodarczyk, Andrzej Węgiel, Aleksandra Osielczak, Maria Możdżan, Laura Biskup, Agata Grochowska, Maria Wołyniak, Dominik Gajewski, Mateusz Porc, Kasper Maryńczak, Łukasz Dziki
    Frontiers in Surgery.2024;[Epub]     CrossRef
  • The game-changing impact of POLE mutations in oncology—a review from a gynecologic oncology perspective
    Johanna Kögl, Teresa L. Pan, Christian Marth, Alain G. Zeimet
    Frontiers in Oncology.2024;[Epub]     CrossRef
  • Progress of Immune Checkpoint Inhibitors Therapy for pMMR/MSS Metastatic Colorectal Cancer
    Fanjie Qu, Shuang Wu, WeiWei Yu
    OncoTargets and Therapy.2024; Volume 17: 1223.     CrossRef
  • Is the combination of immunotherapy with conventional chemotherapy the key to increase the efficacy of colorectal cancer treatment?
    Jonadab E Olguin, Monica G Mendoza-Rodriguez, C Angel Sanchez-Barrera, Luis I Terrazas
    World Journal of Gastrointestinal Oncology.2023; 15(2): 251.     CrossRef
  • Systemic treatment for metastatic colorectal cancer
    Wattana Leowattana, Pathomthep Leowattana, Tawithep Leowattana
    World Journal of Gastroenterology.2023; 29(10): 1425.     CrossRef
  • Systemic treatment for metastatic colorectal cancer
    Wattana Leowattana, Pathomthep Leowattana, Tawithep Leowattana
    World Journal of Gastroenterology.2023; 29(10): 1569.     CrossRef
  • Case report: long-term sustained remission in a case of metastatic colon cancer with high microsatellite instability and KRAS exon 2 p.G12D mutation treated with fruquintinib after local radiotherapy: a case report and literature review
    Ruiqi Wang, Dan Cong, Yuansong Bai, Wenlong Zhang
    Frontiers in Pharmacology.2023;[Epub]     CrossRef
  • Avelumab vs Standard Second-Line Chemotherapy in Patients With Metastatic Colorectal Cancer and Microsatellite Instability
    Julien Taïeb, Olivier Bouche, Thierry André, Karine Le Malicot, Pierre Laurent-Puig, Jérémie Bez, Clémence Toullec, Christophe Borg, Violaine Randrian, Ludovic Evesque, Stéphane Corbinais, Hervé Perrier, Bruno Buecher, Frederic Di Fiore, Claire Gallois, J
    JAMA Oncology.2023; 9(10): 1356.     CrossRef
  • Circulating Tumor DNA Response and Minimal Residual Disease Assessment in DNA Polymerase Epsilon-Mutated Colorectal Cancer Undergoing Immunotherapy
    Areeb Lutfi, Maaz K Afghan, Pashtoon M Kasi
    Cureus.2023;[Epub]     CrossRef
  • Next generation immuno-oncology biomarkers in gastrointestinal cancer: what does the future hold?
    Hassan Abushukair, Obada Ababneh, Ayah Al-Bzour, Ibrahim Halil Sahin, Anwaar Saeed
    Expert Review of Molecular Diagnostics.2023; 23(10): 863.     CrossRef
  • Immunological Assessment of Recent Immunotherapy for Colorectal Cancer
    Subhadeep Das, Diptikanta Acharya
    Immunological Investigations.2023; 52(8): 1065.     CrossRef
  • Immunotherapy with Immune Checkpoint Inhibitors for Advanced Colorectal Cancer: A Promising Individualized Treatment Strategy
    Ying Yang, Wen-Jian Meng, Zi-Qiang Wang
    Frontiers in Bioscience-Landmark.2023;[Epub]     CrossRef
  • Can the tumor-agnostic evaluation of MSI/MMR status be the common denominator for the immunotherapy treatment of patients with several solid tumors?
    Daniele Fanale, Lidia Rita Corsini, Raimondo Scalia, Chiara Brando, Alessandra Cucinella, Giorgio Madonia, Alessandra Dimino, Clarissa Filorizzo, Nadia Barraco, Marco Bono, Alessia Fiorino, Luigi Magrin, Roberta Sciacchitano, Alessandro Perez, Tancredi Di
    Critical Reviews in Oncology/Hematology.2022; 170: 103597.     CrossRef
  • Landscape of Immunotherapy Options for Colorectal Cancer: Current Knowledge and Future Perspectives beyond Immune Checkpoint Blockade
    Alecsandra Gorzo, Diana Galos, Simona Ruxandra Volovat, Cristian Virgil Lungulescu, Claudia Burz, Daniel Sur
    Life.2022; 12(2): 229.     CrossRef
  • Immunotherapy for a POLE Mutation Advanced Non-Small-Cell Lung Cancer Patient
    Yang Fu, Yue Zheng, Pei-Pei Wang, Yue-Yun Chen, Zhen-Yu Ding
    Frontiers in Pharmacology.2022;[Epub]     CrossRef
  • CDK4/6 blockade provides an alternative approach for treatment of mismatch-repair deficient tumors
    Inken Salewski, Julia Henne, Leonie Engster, Paula Krone, Bjoern Schneider, Caterina Redwanz, Heiko Lemcke, Larissa Henze, Christian Junghanss, Claudia Maletzki
    OncoImmunology.2022;[Epub]     CrossRef
  • Predicting immunotherapy outcomes in patients with MSI tumors using NLR and CT global tumor volume
    Younes Belkouchi, Laetitia Nebot-Bral, Littisha Lawrance, Michele Kind, Clémence David, Samy Ammari, Paul-Henry Cournède, Hugues Talbot, Perrine Vuagnat, Cristina Smolenschi, Patricia L. Kannouche, Nathalie Chaput, Nathalie Lassau, Antoine Hollebecque
    Frontiers in Oncology.2022;[Epub]     CrossRef
  • Predictive biomarkers of colon cancer immunotherapy: Present and future
    Wanting Hou, Cheng Yi, Hong Zhu
    Frontiers in Immunology.2022;[Epub]     CrossRef
  • Research Progress in the Treatment of Liver Metastasis from Colon Cancer
    龙坤 郑
    Advances in Clinical Medicine.2022; 12(12): 11179.     CrossRef
  • Recent Advances in Monoclonal Antibody Therapy for Colorectal Cancers
    Kyusang Hwang, Jin Hwan Yoon, Ji Hyun Lee, Sukmook Lee
    Biomedicines.2021; 9(1): 39.     CrossRef
  • Complete Response to Pembrolizumab in Advanced Colon Cancer Harboring Somatic POLE F367S Mutation with Microsatellite Stability Status: A Case Study
    Jianxin Chen, Haizhou Lou
    OncoTargets and Therapy.2021; Volume 14: 1791.     CrossRef
  • Comprehensive tumor molecular profile analysis in clinical practice
    Mustafa Özdoğan, Eirini Papadopoulou, Nikolaos Tsoulos, Aikaterini Tsantikidi, Vasiliki-Metaxa Mariatou, Georgios Tsaousis, Evgenia Kapeni, Evgenia Bourkoula, Dimitrios Fotiou, Georgios Kapetsis, Ioannis Boukovinas, Nikolaos Touroutoglou, Athanasios Fassa
    BMC Medical Genomics.2021;[Epub]     CrossRef
  • Combined vaccine-immune-checkpoint inhibition constitutes a promising strategy for treatment of dMMR tumors
    Inken Salewski, Steffen Kuntoff, Andreas Kuemmel, Rico Feldtmann, Stephan B. Felix, Larissa Henze, Christian Junghanss, Claudia Maletzki
    Cancer Immunology, Immunotherapy.2021; 70(12): 3405.     CrossRef
  • Immune Checkpoint Inhibitor Associated Hepatotoxicity in Primary Liver Cancer Versus Other Cancers: A Systematic Review and Meta‐Analysis
    Jianyang Fu, Wang-Zhong Li, Nicole A. McGrath, Chunwei Walter Lai, Gagandeep Brar, Yan-Qun Xiang, Changqing Xie
    Frontiers in Oncology.2021;[Epub]     CrossRef
  • Liver Immune Microenvironment and Metastasis from Colorectal Cancer-Pathogenesis and Therapeutic Perspectives
    Xuezhen Zeng, Simon E. Ward, Jingying Zhou, Alfred S. L. Cheng
    Cancers.2021; 13(10): 2418.     CrossRef
  • Perspectives on Immunotherapy of Metastatic Colorectal Cancer
    Yongjiu Dai, Wenhu Zhao, Lei Yue, Xinzheng Dai, Dawei Rong, Fan Wu, Jian Gu, Xiaofeng Qian
    Frontiers in Oncology.2021;[Epub]     CrossRef
  • Treatment Efficacy of Immune Checkpoint Inhibitors for Patients with Advanced or Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis
    Junhee Pyo, Hyo-Jung Park
    Journal of Clinical Medicine.2021; 10(16): 3599.     CrossRef
  • Immune-Checkpoint Inhibitors for Metastatic Colorectal Cancer: A Systematic Review of Clinical Outcomes
    Dmitrii Shek, Liia Akhuba, Matteo S. Carlino, Adnan Nagrial, Tania Moujaber, Scott A. Read, Bo Gao, Golo Ahlenstiel
    Cancers.2021; 13(17): 4345.     CrossRef
  • Efficacy of Immune Checkpoint Inhibitors in Patients with Mismatch Repair-Deficient or Microsatellite Instability-High Metastatic Colorectal Cancer: Analysis of Three Phase-II Trials
    Luca Cancanelli, Melania Rivano, Lorenzo Di Spazio, Marco Chiumente, Daniele Mengato, Andrea Messori
    Cureus.2021;[Epub]     CrossRef
  • Molecular Targets for the Treatment of Metastatic Colorectal Cancer
    Romain Cohen, Thomas Pudlarz, Jean-François Delattre, Raphaël Colle, Thierry André
    Cancers.2020; 12(9): 2350.     CrossRef
  • RECIST and iRECIST criteria for the evaluation of nivolumab plus ipilimumab in patients with microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: the GERCOR NIPICOL phase II study
    Romain Cohen, Jaafar Bennouna, Aurélia Meurisse, Christophe Tournigand, Christelle De La Fouchardière, David Tougeron, Christophe Borg, Thibault Mazard, Benoist Chibaudel, Marie-Line Garcia-Larnicol, Magali Svrcek, Dewi Vernerey, Yves Menu, Thierry André
    Journal for ImmunoTherapy of Cancer.2020; 8(2): e001499.     CrossRef
  • Emerging Role of Immunotherapy for Colorectal Cancer with Liver Metastasis


    Xianzhe Yu, Lingling Zhu, Jiewei Liu, Ming Xie, Jiang Chen, Jianguo Li
    OncoTargets and Therapy.2020; Volume 13: 11645.     CrossRef
  • Current status and perspectives of immune checkpoint inhibitors for colorectal cancer
    Hidekazu Hirano, Atsuo Takashima, Tetsuya Hamaguchi, Dai Shida, Yukihide Kanemitsu
    Japanese Journal of Clinical Oncology.2020;[Epub]     CrossRef
  • 13,511 View
  • 490 Download
  • 61 Web of Science
  • 37 Crossref
Close layer
BioPATH: A Biomarker Study in Asian Patients with HER2+ Advanced Breast Cancer Treated with Lapatinib and Other Anti-HER2 Therapy
Sung-Bae Kim, In-Gu Do, Janice Tsang, Tae-You Kim, Yoon-Sim Yap, Gerardo Cornelio, Gyungyub Gong, Soonmyung Paik, Suee Lee, Ting-Ying Ng, Sarah Park, Ho-Suk Oh, Joanne Chiu, Joohyuk Sohn, Moonhee Lee, Young-Jin Choi, Eun Mi Lee, Kyong-Hwa Park, Christos Nathaniel, Jungsil Ro
Cancer Res Treat. 2019;51(4):1527-1539.   Published online June 4, 2019
DOI: https://doi.org/10.4143/crt.2018.598
AbstractAbstract PDFPubReaderePub
Purpose
BioPATH is a non-interventional study evaluating the relationship of molecular biomarkers (PTEN deletion/downregulation, PIK3CA mutation, truncated HER2 receptor [p95HER2], and tumor HER2 mRNA levels) to treatment responses in Asian patients with HER2+ advanced breast cancer treated with lapatinib and other HER2-targeted agents. Materials and Methods Female Asian HER2+ breast cancer patients (n=154) who were candidates for lapatinib-based treatment following metastasis and having an available primary tumor biopsy specimen were included. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, overall survival on lapatinib, correlation between biomarker status and PFS for any previous trastuzumab-based treatment, and conversion/conservation rates of the biomarker status between tissue samples collected at primary diagnosis and at recurrence/metastasis. Potential relationships between tumor mRNA levels of HER2 and response to lapatinib-based therapy were also explored.
Results
p95HER2, PTEN deletion/downregulation, and PIK3CA mutation did not demonstrate any significant co-occurrence pattern and were not predictive of clinical outcomes on either lapatinib-based treatment or any previous trastuzumab-based therapy in the metastatic setting. Proportions of tumors positive for p95HER2 expression, PIK3CA mutation, and PTEN deletion/down-regulation at primary diagnosis were 32%, 31.2%, and 56.2%, respectively. Despite limited availability of paired samples, biomarker status patterns were conserved in most samples. HER2 mRNA levels were not predictive of PFS on lapatinib.
Conclusion
The prevalence of p95HER2 expression, PIK3CA mutation, and PTEN deletion/downregulation at primary diagnosis were similar to previous reports. Importantly, no difference was observed in clinical outcome based on the status of these biomarkers, consistent with reports from other studies.

Citations

Citations to this article as recorded by  
  • PIK3CA Mutation is Associated with Poor Response to HER2-Targeted Therapy in Breast Cancer Patients
    Ju Won Kim, Ah Reum Lim, Ji Young You, Jung Hyun Lee, Sung Eun Song, Nam Kwon Lee, Seung Pil Jung, Kyu Ran Cho, Cheol Yong Kim, Kyong Hwa Park
    Cancer Research and Treatment.2023; 55(2): 531.     CrossRef
  • Discordance of PIK3CA mutational status between primary and metastatic breast cancer: a systematic review and meta-analysis
    Justus Rosin, Ella Svegrup, Antonios Valachis, Ioannis Zerdes
    Breast Cancer Research and Treatment.2023; 201(2): 161.     CrossRef
  • Association of PIK3CA mutation with outcomes in HER2-positive breast cancer treated with anti-HER2 therapy: A meta-analysis and bioinformatic analysis of TCGA‑BRCA data
    Haizhu Chen, Xingbin Hu, Daquan Wang, Ying Wang, Yunfang Yu, Herui Yao
    Translational Oncology.2023; 37: 101738.     CrossRef
  • Comparison of PIK3CA Mutation Prevalence in Breast Cancer Across Predicted Ancestry Populations
    Jessica W. Chen, Karthikeyan Murugesan, Justin Y. Newberg, Ethan S. Sokol, Heidi M. Savage, Thomas J. Stout, Sophia L. Maund, Katherine E. Hutchinson
    JCO Precision Oncology.2022;[Epub]     CrossRef
  • Breast Cancer: A Molecularly Heterogenous Disease Needing Subtype-Specific Treatments
    Ugo Testa, Germana Castelli, Elvira Pelosi
    Medical Sciences.2020; 8(1): 18.     CrossRef
  • 8,704 View
  • 194 Download
  • 4 Web of Science
  • 5 Crossref
Close layer
Impact of Mucin Proportion in the Pretreatment MRI on the Outcomes of Rectal Cancer Patients Undergoing Neoadjuvant Chemoradiotherapy
Eunji Kim, Kyubo Kim, Se Hyung Kim, Sae-Won Han, Tae-You Kim, Seung-Yong Jeong, Kyu Joo Park, Jaemoon Koh, Gyeong Hoon Kang, Eui Kyu Chie
Cancer Res Treat. 2019;51(3):1188-1197.   Published online December 20, 2018
DOI: https://doi.org/10.4143/crt.2018.434
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study was to evaluate treatment response to neoadjuvant chemoradiotherapy (CRT) with regard to mucin status in pathology and pretreatment magnetic resonance imaging (MRI) in locally advanced rectal cancer.
Materials and Methods
Between 2003 and 2011, 306 patients with locally advanced rectal cancer received neoadjuvant CRT followed by surgery, and mucinous adenocarcinoma (MAC) was found in 27 (8.8%). All MAC patients had MRI before and after CRT and mucin proportion at MRI was measured. Therapeutic response was assessed by pathology after total mesorectal excision. To determine the optimal cut-off for mucin proportion in predicting good CRT response (near total or total regression) and negative circumferential resection margin (CRM), the receiver-operating characteristic analysis was performed.
Results
After neoadjuvant CRT, overall downstaging occurred in 44.4% of MAC and 72.4% of non-MAC (p=0.001), and positive CRM (≤1 mm) was observed more frequently in MAC (p<0.001). The optimal threshold for treatment response was 30% for mucin proportion, and there are nine with low mucin proportion (<30%) and 18 with high mucin proportion (≥30%) in pretreatment MRI. Negative CRM and tumor downstaging occurred more common in patients with mucin <30%, although statistically insignificant (p=0.071 and p=0.072, respectively). Regarding oncologic outcomes, lower mucin proportion in pretreatment MRI was associated with better disease-free and overall survival in MAC group (p=0.092 and 0.056, respectively), but the difference did not reach statistical significance.
Conclusion
Poor treatment outcome with neoadjuvant CRT was observed in patients with MAC, especially those with high mucin proportion at pretreatment MRI.

Citations

Citations to this article as recorded by  
  • Mucinous histology is a negative predictor of neoadjuvant chemoradiotherapy for locally advanced rectal adenocarcinoma
    Xiangwen Tan, Yiwei Zhang, Xiaofeng Wu, Qing Fang, Yunhua Xu, Shuxiang Li, Jinyi Yuan, Xiuda Peng, Kai Fu, Shuai Xiao
    BMC Gastroenterology.2024;[Epub]     CrossRef
  • Incomplete Resection Is Twice as Likely in Locally Advanced Mucinous Compared to Nonmucinous Rectal Adenocarcinoma: A National Propensity‐Matched Analysis
    Leah E. Hendrick, Samer Naffouje, Iman Imanirad, Allan Lima Pereira, Tiago Biachi, Julian Sanchez, Sophie Dessureault, Amalia Stefanou, Sean P. Dineen, Seth Felder
    Journal of Surgical Oncology.2024;[Epub]     CrossRef
  • Accelerated T2W Imaging with Deep Learning Reconstruction in Staging Rectal Cancer: A Preliminary Study
    Lan Zhu, Bowen Shi, Bei Ding, Yihan Xia, Kangning Wang, Weiming Feng, Jiankun Dai, Tianyong Xu, Baisong Wang, Fei Yuan, Hailin Shen, Haipeng Dong, Huan Zhang
    Journal of Imaging Informatics in Medicine.2024;[Epub]     CrossRef
  • Mucinous rectal cancers: clinical features and prognosis in a population-based cohort
    Malin Enblad, Klara Hammarström, Joakim Folkesson, Israa Imam, Milan Golubovik, Bengt Glimelius
    BJS Open.2022;[Epub]     CrossRef
  • Mucin-Containing Rectal Cancer: A Review of Unique Imaging, Pathology, and Therapeutic Response Features
    David D. Childs, Caio Max Sao Pedro Rocha Lima, Yi Zhou
    Seminars in Roentgenology.2021; 56(2): 186.     CrossRef
  • Advances in radiological staging of colorectal cancer
    R.J. Goiffon, A. O'Shea, M.G. Harisinghani
    Clinical Radiology.2021; 76(12): 879.     CrossRef
  • A Comprehensive Evaluation of Associations Between Routinely Collected Staging Information and The Response to (Chemo)Radiotherapy in Rectal Cancer
    Klara Hammarström, Israa Imam, Artur Mezheyeuski, Joakim Ekström, Tobias Sjöblom, Bengt Glimelius
    Cancers.2020; 13(1): 16.     CrossRef
  • 8,644 View
  • 174 Download
  • 7 Web of Science
  • 7 Crossref
Close layer
Treatment Patterns and Changes in Quality of Life during First-Line Palliative Chemotherapy in Korean Patients with Advanced Gastric Cancer
Jin Won Kim, Jong Gwang Kim, Byung Woog Kang, Ik-Joo Chung, Young Seon Hong, Tae-You Kim, Hong Suk Song, Kyung Hee Lee, Dae Young Zang, Yoon Ho Ko, Eun-Kee Song, Jin Ho Baek, Dong‐Hoe Koo, So Yeon Oh, Hana Cho, Keun-Wook Lee
Cancer Res Treat. 2019;51(1):223-239.   Published online October 19, 2018
DOI: https://doi.org/10.4143/crt.2018.073
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The purpose of this study was to evaluate chemotherapy patterns and changes in quality of life (QOL) during first-line palliative chemotherapy for Korean patients with unresectable or metastatic/recurrent gastric cancer (GC).
Materials and Methods
Thiswas a non-interventional, multi-center, prospective, observational study of 527 patients in Korea. QOL assessments were conducted using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires (QLQ)-C30 and QLQ-STO22 every 3 months over a 12-month period during first-line palliative chemotherapy. The specific chemotherapy regimens were selected by individual clinicians.
Results
Most patients (93.2%) received combination chemotherapy (mainly fluoropyrimidine plus platinum) as their first-line palliative chemotherapy. The median progression-free survival and overall survival were 8.2 and 14.8 months, respectively. Overall, “a little” changes (differences of 5-10 points from baseline)were observed in some of the functioning or symptom scales; none of the QOL scales showed either “moderate” or “very much” change (i.e., ≥ 11 point difference from baseline). When examining the best change in each QOL domain from baseline, scales related to some aspects of functioning, global health status/QOL, and most symptoms revealed significant improvements (p < 0.05). Throughout the course of first-line palliative chemotherapy, most patients’ QOL was maintained to a similar degree, regardless of their actual response to chemotherapy.
Conclusion
This observational study provides important information on the chemotherapy patterns and QOL changes in Korean patientswith advanced GC. Overall, first-line palliative chemotherapy was found to maintain QOL, and most parameters showed an improvement compared with the baseline at some point during the course.

Citations

Citations to this article as recorded by  
  • Health-related quality of life with bemarituzumab plus mFOLFOX6 in patients with FGFR2b-overexpressing, advanced gastric or gastroesophageal junction cancer
    Z.A. Wainberg, P.C. Enzinger, S. Qin, K. Yamaguchi, J. Wang, X. Zhou, A. Gnanasakthy, K. Taylor, A. Yusuf, I. Majer, A. Jamotte, Y.-K. Kang
    ESMO Gastrointestinal Oncology.2024; 6: 100095.     CrossRef
  • Impact of systemic cancer treatment on quality of life and mental well-being: a comparative analysis of patients with localized and advanced cancer
    Adán Rodríguez-Gonzalez, Alberto Carmona-Bayonas, Raquel Hernandez San Gil, Patricia Cruz-Castellanos, Mónica Antoñanzas-Basa, David Lorente-Estelles, María Jose Corral, Manuel González-Moya, Oscar Alfredo Castillo-Trujillo, Emilio Esteban, Paula Jiménez-
    Clinical and Translational Oncology.2023; 25(12): 3492.     CrossRef
  • Reminiscence therapy-based care program alleviates anxiety and depression, as well as improves the quality of life in recurrent gastric cancer patients
    Xing Wu, Weiwei Zhang
    Frontiers in Psychology.2023;[Epub]     CrossRef
  • Toxicities and Quality of Life during Cancer Treatment in Advanced Solid Tumors
    Eun Mi Lee, Paula Jiménez-Fonseca, Rocio Galán-Moral, Sara Coca-Membribes, Ana Fernández-Montes, Elena Sorribes, Esmeralda García-Torralba, Laura Puntí-Brun, Mireia Gil-Raga, Juana Cano-Cano, Caterina Calderon
    Current Oncology.2023; 30(10): 9205.     CrossRef
  • Psychosocial functioning in individuals with advanced oesophago-gastric cancer: a mixed methods systematic review
    Cara Ghiglieri, Martin Dempster, Sam Wright, Lisa Graham-Wisener
    BMC Palliative Care.2023;[Epub]     CrossRef
  • Multicenter phase III trial of S-1 and cisplatin versus S-1 and oxaliplatin combination chemotherapy for first-line treatment of advanced gastric cancer (SOPP trial)
    Keun-Wook Lee, Ik-Joo Chung, Min-Hee Ryu, Young Iee Park, Byung-Ho Nam, Ho-Suk Oh, Kyung Hee Lee, Hye Sook Han, Bong-Gun Seo, Jae-Cheol Jo, Hyo Rak Lee, Jin Won Kim, Sook Ryun Park, Sang Hee Cho, Yoon-Koo Kang
    Gastric Cancer.2021; 24(1): 156.     CrossRef
  • Effect of early tumor response on the health-related quality of life among patients on second-line chemotherapy for advanced gastric cancer in the ABSOLUTE trial
    Kazumasa Fujitani, Kohei Shitara, Atsuo Takashima, Keisuke Koeda, Hiroki Hara, Norisuke Nakayama, Shuichi Hironaka, Kazuhiro Nishikawa, Yutaka Kimura, Kenji Amagai, Hisashi Hosaka, Yoshito Komatsu, Ken Shimada, Ryohei Kawabata, Hideki Ohdan, Yasuhiro Kode
    Gastric Cancer.2021; 24(2): 467.     CrossRef
  • Quality-of-Life Assessment in Patients Receiving Palliative Chemotherapy: Call for Action
    Maheswari Senthil
    Annals of Surgical Oncology.2021; 28(1): 7.     CrossRef
  • Impact of gastric cancer treatment on quality of life of patients
    Kerstin Schütte, Christian Schulz, Kristina Middelberg-Bisping
    Best Practice & Research Clinical Gastroenterology.2021; 50-51: 101727.     CrossRef
  • Influencing Factors and Effects of Treatment on Quality of Life in Patients With Gastric Cancer—A Systematic Review
    Sophia Kristina Rupp, Andreas Stengel
    Frontiers in Psychiatry.2021;[Epub]     CrossRef
  • Chronological changes in quality of life and body composition after gastrectomy for locally advanced gastric cancer
    Ki Bum Park, Ji Yeon Park, Seung Soo Lee, Ho Young Chung, Oh Kyoung Kwon
    Annals of Surgical Treatment and Research.2020; 98(5): 262.     CrossRef
  • Viennese risk prediction score for Advanced Gastroesophageal carcinoma based on Alarm Symptoms (VAGAS score): characterisation of alarm symptoms in advanced gastro-oesophageal cancer and its correlation with outcome
    Hannah Christina Puhr, Eleonore Pablik, Anna Sophie Berghoff, Gerd Jomrich, Sebastian Friedrich Schoppmann, Matthias Preusser, Aysegül Ilhan-Mutlu
    ESMO Open.2020; 5(2): e000623.     CrossRef
  • 11,855 View
  • 237 Download
  • 12 Web of Science
  • 12 Crossref
Close layer
NFATC3PLA2G15 Fusion Transcript Identified by RNA Sequencing Promotes Tumor Invasion and Proliferation in Colorectal Cancer Cell Lines
Jee-Eun Jang, Hwang-Phill Kim, Sae-Won Han, Hoon Jang, Si-Hyun Lee, Sang-Hyun Song, Duhee Bang, Tae-You Kim
Cancer Res Treat. 2019;51(1):391-401.   Published online June 14, 2018
DOI: https://doi.org/10.4143/crt.2018.103
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study was designed to identify novel fusion transcripts (FTs) and their functional significance in colorectal cancer (CRC) lines.
Materials and Methods
We performed paired-end RNA sequencing of 28 CRC cell lines. FT candidates were identified using TopHat-fusion, ChimeraScan, and FusionMap tools and further experimental validation was conducted through reverse transcription-polymerase chain reaction and Sanger sequencing. FT was depleted in human CRC line and the effects on cell proliferation, cell migration, and cell invasion were analyzed.
Results
One thousand three hundred eighty FT candidates were detected through bioinformatics filtering. We selected six candidate FTs, including four inter-chromosomal and two intrachromosomal FTs and each FT was found in at least one of the 28 cell lines. Moreover, when we tested 19 pairs of CRC tumor and adjacent normal tissue samples, NFATC3PLA2G15 FT was found in two. Knockdown of NFATC3PLA2G15 using siRNA reduced mRNA expression of epithelial–mesenchymal transition (EMT) markers such as vimentin, twist, and fibronectin and increased mesenchymal–epithelial transition markers of E-cadherin, claudin-1, and FOXC2 in colo-320 cell line harboring NFATC3PLA2G15 FT. The NFATC3PLA2G15 knockdown also inhibited invasion, colony formation capacity, and cell proliferation.
Conclusion
These results suggest that that NFATC3PLA2G15 FTs may contribute to tumor progression by enhancing invasion by EMT and proliferation.

Citations

Citations to this article as recorded by  
  • Whole transcriptome analysis identifies ALB-EEF1A1 fusion as a novel biomarker in metastatic colorectal cancer
    Deeksha Rikhari, Ankit Srivastava, Sandhya Rai, Mubashra, Srinivas Patnaik, Sameer Srivastava
    Cancer Pathogenesis and Therapy.2025;[Epub]     CrossRef
  • Nuclear Factor of Activated T Cells (NFAT) Proteins as Targeted Molecules in Diseases: A Narrative Review
    Mohadese Mozafari, Siti Nurnasihah Md Hashim, Khairul Bariah Ahmad Amin Noordin, Siti Aishah Zainal, Ahmad Azlina
    Cureus.2024;[Epub]     CrossRef
  • Identification of predictive markers in the cerebrospinal fluid of patients with glioblastoma
    N. E. Arnotskaya, T. I. Kushnir, I. A. Kudryavtsev, A. A. Mitrofanov, A. Kh. Bekyashev, V. E. Shevchenko
    Advances in Molecular Oncology.2023; 10(2): 117.     CrossRef
  • Murine leukemia virus (MLV) P50 protein induces cell transformation via transcriptional regulatory function
    Charbel Akkawi, Jerome Feuillard, Felipe Leon Diaz, Khalid Belkhir, Nelly Godefroy, Jean-Marie Peloponese, Marylene Mougel, Sebastien Laine
    Retrovirology.2023;[Epub]     CrossRef
  • Unearthing novel fusions as therapeutic targets in solid tumors using targeted RNA sequencing
    Sungbin An, Hyun Hee Koh, Eun Sol Chang, Juyoung Choi, Ji-Young Song, Mi-Sook Lee, Yoon-La Choi
    Frontiers in Oncology.2022;[Epub]     CrossRef
  • Multi-Omics Approaches in Colorectal Cancer Screening and Diagnosis, Recent Updates and Future Perspectives
    Ihsan Ullah, Le Yang, Feng-Ting Yin, Ye Sun, Xing-Hua Li, Jing Li, Xi-Jun Wang
    Cancers.2022; 14(22): 5545.     CrossRef
  • Transcriptome Analysis Reveals MFGE8-HAPLN3 Fusion as a Novel Biomarker in Triple-Negative Breast Cancer
    Meng-Yuan Wang, Man Huang, Chao-Yi Wang, Xiao-Ying Tang, Jian-Gen Wang, Yong-De Yang, Xin Xiong, Chao-Wei Gao
    Frontiers in Oncology.2021;[Epub]     CrossRef
  • Read-through transcripts in lung: germline genetic regulation and correlation with the expression of other genes
    Davide Maspero, Alice Dassano, Giulia Pintarelli, Sara Noci, Loris De Cecco, Matteo Incarbone, Davide Tosi, Luigi Santambrogio, Tommaso A Dragani, Francesca Colombo
    Carcinogenesis.2020; 41(7): 918.     CrossRef
  • Blocking NFATc3 ameliorates azoxymethane/dextran sulfate sodium induced colitis-associated colorectal cancer in mice via the inhibition of inflammatory responses and epithelial-mesenchymal transition
    Yan Lin, Moussa Harouna Koumba, Suxuan Qu, Dongxu Wang, Lianjie Lin
    Cellular Signalling.2020; 74: 109707.     CrossRef
  • Omics technologies for improved diagnosis and treatment of colorectal cancer: Technical advancement and major perspectives
    Nishu Dalal, Rekha Jalandra, Minakshi Sharma, Hridayesh Prakash, Govind K. Makharia, Pratima R. Solanki, Rajeev Singh, Anil Kumar
    Biomedicine & Pharmacotherapy.2020; 131: 110648.     CrossRef
  • Fusion Transcripts of Adjacent Genes: New Insights into the World of Human Complex Transcripts in Cancer
    Vincenza Barresi, Ilaria Cosentini, Chiara Scuderi, Salvatore Napoli, Virginia Di Bella, Giorgia Spampinato, Daniele Filippo Condorelli
    International Journal of Molecular Sciences.2019; 20(21): 5252.     CrossRef
  • The Landscape of Actionable Gene Fusions in Colorectal Cancer
    Filippo Pagani, Giovanni Randon, Vincenzo Guarini, Alessandra Raimondi, Michele Prisciandaro, Riccardo Lobefaro, Maria Di Bartolomeo, Gabriella Sozzi, Filippo de Braud, Patrizia Gasparini, Filippo Pietrantonio
    International Journal of Molecular Sciences.2019; 20(21): 5319.     CrossRef
  • Exploring disease-specific methylated CpGs in human male genital abnormalities by using methylated-site display-amplified fragment length polymorphism (MSD-AFLP)
    Toshiki AIBA, Toshiyuki SAITO, Akiko HAYASHI, Shinji SATO, Harunobu YUNOKAWA, Maki FUKAMI, Yutaro HAYASHI, Kentaro MIZUNO, Yuichi SATO, Yoshiyuki KOJIMA, Seiichiroh OHSAKO
    Journal of Reproduction and Development.2019; 65(6): 491.     CrossRef
  • 10,007 View
  • 278 Download
  • 13 Web of Science
  • 13 Crossref
Close layer
Phase I Dose-Finding Study of OPB-111077, a Novel STAT3 Inhibitor, in Patients with Advanced Hepatocellular Carcinoma
Changhoon Yoo, Jihoon Kang, Ho Yeong Lim, Jee Hyun Kim, Myung-Ah Lee, Kyung-Hun Lee, Tae-You Kim, Baek-Yeol Ryoo
Cancer Res Treat. 2019;51(2):510-518.   Published online June 13, 2018
DOI: https://doi.org/10.4143/crt.2018.226
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The signal transducer and activator of transcription 3 (STAT3) signaling pathway might be a promising therapeutic target for hepatocellular carcinoma (HCC).
Materials and Methods
This study was a multicenter, open-label, non-comparative, dose escalating phase I study of OPB-111077, an oral STAT3 inhibitor, in patients with advanced HCC who failed on sorafenib. Continuous dosing (daily administration, 50 to 400 mg) and intermittent dosing (4-days on/3-days off administration: 300 to 900 mg) regimens were evaluated and the dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and recommended dose (RD) were the primary endpoints.
Results
A total of 33 patients (19 for continuous dosing and 14 for intermittent dosing) were enrolled. One patient experienced a DLT with grade 3 dizziness, but the MTD was identified in neither the continuous nor the intermittent dosing cohorts. The RDs were determined to be 250 mg for the continuous dosing regimen and 600 mg for the intermittent dosing regimen. There was no treatment-related death; five patients (15.2%) had grade 3-4 toxicities including thrombocytopenia (6%), fatigue (3%), and dizziness (3%). No patients achieved complete or partial responses and the median progression-free survival was 1.4 months (95% confidence interval, 0.8 to 2.8).
Conclusion
OPB-111077 was well tolerated in patients with advanced HCC after sorafenib failure, but only showed limited preliminary efficacy outcomes. Further investigation of the role of the STAT3 signaling pathway in HCC and the development of biomarkers for STAT3 inhibitors are warranted.

Citations

Citations to this article as recorded by  
  • Mechanisms and therapeutic prospect of the JAK-STAT signaling pathway in liver cancer
    JunJun Jia, Xuelian Zhou, Qingfei Chu
    Molecular and Cellular Biochemistry.2025; 480(1): 1.     CrossRef
  • Structural Optimization and Characterization of Highly Potent and Selective STAT3 Inhibitors for the Treatment of Triple Negative Breast Cancer
    Wangrui Jin, Yuzhu Zhang, Baozhen Wang, Zhaoyong Kang, Huachao Li, Jingfeng Song, Yihua Chen, Hai Xiong, Jing Chen
    European Journal of Medicinal Chemistry.2025; : 117332.     CrossRef
  • Hepatocellular carcinoma: signaling pathways and therapeutic advances
    Jiaojiao Zheng, Siying Wang, Lei Xia, Zhen Sun, Kui Ming Chan, René Bernards, Wenxin Qin, Jinhong Chen, Qiang Xia, Haojie Jin
    Signal Transduction and Targeted Therapy.2025;[Epub]     CrossRef
  • Precision therapeutic targets for HPV-positive cancers: an overview and new insights
    Yixi Huang, Jiayi Wang, Wenbin Yang, Feifei Hou, Xiaodong Feng
    Infectious Agents and Cancer.2025;[Epub]     CrossRef
  • Targeting JAK2/STAT3 for the treatment of cancer: A review on recent advancements in molecular development using structural analysis and SAR investigations
    Rupali Kohal, Priya Bisht, Ghanshyam Das Gupta, Sant Kumar Verma
    Bioorganic Chemistry.2024; 143: 107095.     CrossRef
  • Unraveling the complexity of STAT3 in cancer: molecular understanding and drug discovery
    Yamei Hu, Zigang Dong, Kangdong Liu
    Journal of Experimental & Clinical Cancer Research.2024;[Epub]     CrossRef
  • Hepatocellular Carcinoma: Old and Emerging Therapeutic Targets
    Greta Pessino, Claudia Scotti, Maristella Maggi
    Cancers.2024; 16(5): 901.     CrossRef
  • Isoalantolactone exerts anti‐melanoma effects via inhibiting PI3K/AKT/mTOR and STAT3 signaling in cell and mouse models
    Jun‐Kui Li, Xiao‐Li Jiang, Zhu Zhang, Wen‐Qing Chen, Jun‐Jie Peng, Bin Liu, Pei‐Li Zhu, Ken‐Kin‐Lam Yung
    Phytotherapy Research.2024; 38(6): 2800.     CrossRef
  • Prognostic and therapeutic potential of STAT3: Opportunities and challenges in targeting HPV-mediated cervical carcinogenesis
    Divya Janjua, Kulbhushan Thakur, Nikita Aggarwal, Apoorva Chaudhary, Joni Yadav, Arun Chhokar, Tanya Tripathi, Udit Joshi, Anna Senrung, Alok Chandra Bharti
    Critical Reviews in Oncology/Hematology.2024; 197: 104346.     CrossRef
  • Signaling pathways in liver cancer: pathogenesis and targeted therapy
    Yangtao Xue, Yeling Ruan, Yali Wang, Peng Xiao, Junjie Xu
    Molecular Biomedicine.2024;[Epub]     CrossRef
  • STAT3: Key targets of growth-promoting receptor positive breast cancer
    Rui-yuan Jiang, Jia-yu Zhu, Huan-ping Zhang, Yuan Yu, Zhi-xin Dong, Huan-huan Zhou, Xiaojia Wang
    Cancer Cell International.2024;[Epub]     CrossRef
  • Discovery, Optimization, and Evaluation of Novel N-(Benzimidazol-5-yl)-1,3,4-thiadiazol-2-amine Analogues as Potent STAT3 Inhibitors for Cancer Treatment
    Ru Wang, Ting-Ting Du, Wen-Qiang Liu, Yi-Chen Liu, Ya-Dong Yang, Jin-Ping Hu, Ming Ji, Bei-Bei Yang, Li Li, Xiao-Guang Chen
    Journal of Medicinal Chemistry.2023; 66(17): 12373.     CrossRef
  • Polyphenols as potential metabolism mechanisms regulators in liver protection and liver cancer prevention
    Shuangfeng Li, Shuangshuang Yin, Hui Ding, Yingying Shao, Shiyue Zhou, Weiling Pu, Lifeng Han, Tao Wang, Haiyang Yu
    Cell Proliferation.2023;[Epub]     CrossRef
  • Eupalinolide J Inhibits Cancer Metastasis by Promoting STAT3 Ubiquitin-Dependent Degradation
    Hongtao Hu, Haoyang Bai, Lili Huang, Bo Yang, Huajun Zhao
    Molecules.2023; 28(7): 3143.     CrossRef
  • Discovery of a Highly Potent and Orally Bioavailable STAT3 Dual Phosphorylation Inhibitor for Pancreatic Cancer Treatment
    Peng He, Aiwu Bian, Ying Miao, Wangrui Jin, Huang Chen, Jia He, Liting Li, Yue Sun, Jiangnan Ye, Mingyao Liu, Zhengfang Yi, Wenbo Zhou, Yihua Chen
    Journal of Medicinal Chemistry.2022; 65(22): 15487.     CrossRef
  • STAT3 pathway in cancers: Past, present, and future
    Han‐Qi Wang, Qi‐Wen Man, Fang‐Yi Huo, Xin Gao, Hao Lin, Su‐Ran Li, Jing Wang, Fu‐Chuan Su, Lulu Cai,, Yi Shi, Bing Liu,, Lin‐Lin Bu
    MedComm.2022;[Epub]     CrossRef
  • Systemic Therapy for Hepatocellular Carcinoma: Current Updates and Outlook
    Yinjie Fan, Hang Xue, Huachuan Zheng
    Journal of Hepatocellular Carcinoma.2022; Volume 9: 233.     CrossRef
  • Constant Activation of STAT3 Contributes to the Development of Adenomyosis in Females
    Takehiro Hiraoka, Yasushi Hirota, Shizu Aikawa, Rei Iida, Chihiro Ishizawa, Tetsuaki Kaku, Tomoyuki Hirata, Yamato Fukui, Shun Akaeda, Mitsunori Matsuo, Ryoko Shimizu-Hirota, Norihiko Takeda, Yutaka Osuga
    Endocrinology.2022;[Epub]     CrossRef
  • Biomarker‑driven phase Ib clinical trial of OPB‑111077 in acute myeloid leukemia
    Joaquín Martínez‑López, Pau Montesinos, Nieves López‑Muñoz, Rosa Ayala, Pilar Martínez‑Sánchez, Julian Gorrochategui, José Rojas‑Rudilla, Daniel Primo, Juan-Miguel Bergua‑Burgues, María Calbacho, Evelyn Acuña‑Cruz, José Pérez‑Simón, Adolfo De La Fuente, J
    Medicine International.2022;[Epub]     CrossRef
  • Novel STAT3 Inhibitors Targeting STAT3 Dimerization by Binding to the STAT3 SH2 Domain
    Yaping Hua, Xing Yuan, Yun-heng Shen, Jinxin Wang, Waqas Azeem, Shuo Yang, Alexandra Gade, Seyed Mohammad Lellahi, Anne Margrete Øyan, Xisong Ke, Wei-dong Zhang, Karl-Henning Kalland
    Frontiers in Pharmacology.2022;[Epub]     CrossRef
  • Discovery of a Novel Potent STAT3 Inhibitor HP590 with Dual p-Tyr705/Ser727 Inhibitory Activity for Gastric Cancer Treatment
    Peng He, Ying Miao, Yue Sun, Aiwu Bian, Wangrui Jin, Huang Chen, Jiangnan Ye, Jia He, Yangrui Peng, Haijun Gu, Mingyao Liu, Zhengfang Yi, Yihua Chen
    Journal of Medicinal Chemistry.2022; 65(19): 12650.     CrossRef
  • STAT3 and Its Targeting Inhibitors in Oral Squamous Cell Carcinoma
    Mingjing Jiang, Bo Li
    Cells.2022; 11(19): 3131.     CrossRef
  • NAFLD and HBV interplay - related mechanisms underlying liver disease progression
    Evanthia Tourkochristou, Stelios F. Assimakopoulos, Konstantinos Thomopoulos, Markos Marangos, Christos Triantos
    Frontiers in Immunology.2022;[Epub]     CrossRef
  • An update on investigational therapies that target STAT3 for the treatment of cancer
    Matteo Santoni, Francesca Miccini, Alessia Cimadamore, Francesco Piva, Francesco Massari, Liang Cheng, Antonio Lopez-Beltran, Rodolfo Montironi, Nicola Battelli
    Expert Opinion on Investigational Drugs.2021; 30(3): 245.     CrossRef
  • Rational drug design of benzothiazole-based derivatives as potent signal transducer and activator of transcription 3 (STAT3) signaling pathway inhibitors
    Dingding Gao, Nan Jin, Yixian Fu, Yueyue Zhu, Yujie Wang, Ting Wang, Yuehong Chen, Mingming Zhang, Qiang Xiao, Min Huang, Yingxia Li
    European Journal of Medicinal Chemistry.2021; 216: 113333.     CrossRef
  • NAFLD-Associated HCC: Progress and Opportunities
    Daniel Geh, Quentin M Anstee, Helen L Reeves
    Journal of Hepatocellular Carcinoma.2021; Volume 8: 223.     CrossRef
  • The therapeutic potential of mitochondrial toxins
    Manabu Kawada, Masahide Amemiya, Junjiro Yoshida, Tomokazu Ohishi
    The Journal of Antibiotics.2021; 74(10): 696.     CrossRef
  • Advances of Targeted Therapy for Hepatocellular Carcinoma
    Mengke Niu, Ming Yi, Ning Li, Kongju Wu, Kongming Wu
    Frontiers in Oncology.2021;[Epub]     CrossRef
  • Mitochondrial Plasticity Promotes Resistance to Sorafenib and Vulnerability to STAT3 Inhibition in Human Hepatocellular Carcinoma
    Shusil K. Pandit, Giada Sandrini, Jessica Merulla, Valentina Nobili, Xin Wang, Alessia Zangari, Andrea Rinaldi, Dheeraj Shinde, Giuseppina M. Carbone, Carlo V. Catapano
    Cancers.2021; 13(23): 6029.     CrossRef
  • Phosphotyrosine isosteres: past, present and future
    Robert A. Cerulli, Joshua A. Kritzer
    Organic & Biomolecular Chemistry.2020; 18(4): 583.     CrossRef
  • Rewiring Host Signaling: Hepatitis C Virus in Liver Pathogenesis
    Alessia Virzì, Armando Andres Roca Suarez, Thomas F. Baumert, Joachim Lupberger
    Cold Spring Harbor Perspectives in Medicine.2020; 10(1): a037366.     CrossRef
  • Quinazoline Ligands Induce Cancer Cell Death through Selective STAT3 Inhibition and G-Quadruplex Stabilization
    Jan Jamroskovic, Mara Doimo, Karam Chand, Ikenna Obi, Rajendra Kumar, Kristoffer Brännström, Mattias Hedenström, Rabindra Nath Das, Almaz Akhunzianov, Marco Deiana, Kazutoshi Kasho, Sebastian Sulis Sato, Parham L. Pourbozorgi, James E. Mason, Paolo Medini
    Journal of the American Chemical Society.2020; 142(6): 2876.     CrossRef
  • JAK/STAT signaling in hepatocellular carcinoma
    Justin Jit Hin Tang, Dexter Kai Hao Thng, Jhin Jieh Lim, Tan Boon Toh
    Hepatic Oncology.2020;[Epub]     CrossRef
  • Targeting apoptosis in cancer therapy
    Benedito A. Carneiro, Wafik S. El-Deiry
    Nature Reviews Clinical Oncology.2020; 17(7): 395.     CrossRef
  • Targeting acute myeloid leukemia stem cells: Current therapies in development and potential strategies with new dimensions
    Yuxin Tan, Qiuji Wu, Fuling Zhou
    Critical Reviews in Oncology/Hematology.2020; 152: 102993.     CrossRef
  • Manipulation of JAK/STAT Signalling by High-Risk HPVs: Potential Therapeutic Targets for HPV-Associated Malignancies
    Ethan L. Morgan, Andrew Macdonald
    Viruses.2020; 12(9): 977.     CrossRef
  • STAT3 inhibition protects against neuroinflammation and BACE1 upregulation induced by systemic inflammation
    Périne Millot, Carine San, Evangeline Bennana, Baptiste Porte, Nicolas Vignal, Jacques Hugon, Claire Paquet, Benoit Hosten, François Mouton-Liger
    Immunology Letters.2020; 228: 129.     CrossRef
  • STAT3 Inhibitor OPB-51602 Is Cytotoxic to Tumor Cells Through Inhibition of Complex I and ROS Induction
    Lara Brambilla, Tanaya Lahiri, Michael Cammer, David E. Levy
    iScience.2020; 23(12): 101822.     CrossRef
  • Systemic Therapy for Hepatocellular Carcinoma: Advances and Hopes
    Chen-Hao Zhang, Ming Li, You-Pei Lin, Qiang Gao
    Current Gene Therapy.2020; 20(2): 84.     CrossRef
  • STAT3 as a potential therapeutic target in triple negative breast cancer: a systematic review
    Jiang-Jiang Qin, Li Yan, Jia Zhang, Wei-Dong Zhang
    Journal of Experimental & Clinical Cancer Research.2019;[Epub]     CrossRef
  • Recent Insights Into the Multiple Pathways Driving Non-alcoholic Steatohepatitis-Derived Hepatocellular Carcinoma
    Kazuki Takakura, Tsunekazu Oikawa, Masanori Nakano, Chisato Saeki, Yuichi Torisu, Mikio Kajihara, Masayuki Saruta
    Frontiers in Oncology.2019;[Epub]     CrossRef
  • Direct Targeting Options for STAT3 and STAT5 in Cancer
    Anna Orlova, Christina Wagner, Elvin D. de Araujo, Dávid Bajusz, Heidi A. Neubauer, Marco Herling, Patrick T. Gunning, György M. Keserű, Richard Moriggl
    Cancers.2019; 11(12): 1930.     CrossRef
  • 10,914 View
  • 316 Download
  • 42 Web of Science
  • 42 Crossref
Close layer
Landscape of Actionable Genetic Alterations Profiled from 1,071 Tumor Samples in Korean Cancer Patients
Se-Hoon Lee, Boram Lee, Joon Ho Shim, Kwang Woo Lee, Jae Won Yun, Sook-Young Kim, Tae-You Kim, Yeul Hong Kim, Young Hyeh Ko, Hyun Cheol Chung, Chang Sik Yu, Jeeyun Lee, Sun Young Rha, Tae Won Kim, Kyung Hae Jung, Seock-Ah Im, Hyeong-Gon Moon, Sukki Cho, Jin Hyoung Kang, Jihun Kim, Sang Kyum Kim, Han Suk Ryu, Sang Yun Ha, Jong Il Kim, Yeun-Jun Chung, Cheolmin Kim, Hyung-Lae Kim, Woong-Yang Park, Dong-Young Noh, Keunchil Park
Cancer Res Treat. 2019;51(1):211-222.   Published online April 23, 2018
DOI: https://doi.org/10.4143/crt.2018.132
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
With the emergence of next-generation sequencing (NGS) technology, profiling a wide range of genomic alterations has become a possibility resulting in improved implementation of targeted cancer therapy. In Asian populations, the prevalence and spectrum of clinically actionable genetic alterations has not yet been determined because of a lack of studies examining high-throughput cancer genomic data.
Materials and Methods
To address this issue, 1,071 tumor samples were collected from five major cancer institutes in Korea and analyzed using targeted NGS at a centralized laboratory. Samples were either fresh frozen or formalin-fixed, paraffin embedded (FFPE) and the quality and yield of extracted genomic DNA was assessed. In order to estimate the effect of sample condition on the quality of sequencing results, tissue preparation method, specimen type (resected or biopsied) and tissue storage time were compared.
Results
We detected 7,360 non-synonymous point mutations, 1,164 small insertions and deletions, 3,173 copy number alterations, and 462 structural variants. Fifty-four percent of tumors had one or more clinically relevant genetic mutation. The distribution of actionable variants was variable among different genes. Fresh frozen tissues, surgically resected specimens, and recently obtained specimens generated superior sequencing results over FFPE tissues, biopsied specimens, and tissues with long storage duration.
Conclusion
In order to overcome, challenges involved in bringing NGS testing into routine clinical use, a centralized laboratory model was designed that could improve the NGS workflows, provide appropriate turnaround times and control costs with goal of enabling precision medicine.

Citations

Citations to this article as recorded by  
  • Clinical implementation of next-generation sequencing testing and genomically-matched therapy: a real-world data in a tertiary hospital
    Jin Won Kim, Hee Young Na, Sejoon Lee, Ji-Won Kim, Koung Jin Suh, Se Hyun Kim, Yu Jung Kim, Keun-Wook Lee, Jong Seok Lee, Jaihwan Kim, Jin-Hyeok Hwang, Kihwan Hwang, Chae-Yong Kim, Yong Beom Kim, Soomin Ahn, Kyu Sang Lee, Hyojin Kim, Hye Seung Lee, So Yeo
    Scientific Reports.2025;[Epub]     CrossRef
  • Real-World Data and Clinical Implications of Next-Generation Sequencing (NGS)-Based Analysis in Metastatic Breast Cancer Patients
    Fabio Canino, Antonio Tornincasa, Stefania Bettelli, Samantha Manfredini, Monica Barbolini, Luca Moscetti, Claudia Omarini, Angela Toss, Fabio Tamburrano, Giuseppina Antonelli, Federica Baglio, Lorenzo Belluzzi, Giulio Martinelli, Salvatore Natalizio, Orn
    International Journal of Molecular Sciences.2024; 25(5): 2490.     CrossRef
  • Exploring the DNA methylome of Korean patients with colorectal cancer consolidates the clinical implications of cancer-associated methylation markers
    Sejoon Lee, Kil-yong Lee, Ji-Hwan Park, Duck-Woo Kim, Heung-Kwon Oh, Seong-Taek Oh, Jongbum Jeon, Dongyoon Lee, Soobok Joe, Hoang Bao Khanh Chu, Jisun Kang, Jin-Young Lee, Sheehyun Cho, Hyeran Shim, Si-Cho Kim, Hong Seok Lee, Young-Joon Kim, Jin Ok Yang,
    BMB Reports.2024; 57(3): 161.     CrossRef
  • Establishing molecular pathology curriculum for pathology trainees and continued medical education: a collaborative work from the Molecular Pathology Study Group of the Korean Society of Pathologists
    Jiwon Koh, Ha Young Park, Jeong Mo Bae, Jun Kang, Uiju Cho, Seung Eun Lee, Haeyoun Kang, Min Eui Hong, Jae Kyung Won, Youn-La Choi, Wan-Seop Kim, Ahwon Lee
    Journal of Pathology and Translational Medicine.2023; 57(5): 265.     CrossRef
  • Quality and Quantity of Nucleic Acids Extracted from Formalin-Fixed Paraffin-Embedded Lymphoma Biopsies from Nigerian Archived Biopsy
    IC Uzoma, IA Taiwo, NI Ugwu, MA Durosinmi, O Akinloye
    Nigerian Journal of Clinical Practice.2023; 26(12): 1854.     CrossRef
  • Recommendations for the Use of Next-Generation Sequencing and the Molecular Tumor Board for Patients with Advanced Cancer: A Report from KSMO and KCSG Precision Medicine Networking Group
    Shinkyo Yoon, Miso Kim, Yong Sang Hong, Han Sang Kim, Seung Tae Kim, Jihun Kim, Hongseok Yun, Changhoon Yoo, Hee Kyung Ahn, Hyo Song Kim, In Hee Lee, In-Ho Kim, Inkeun Park, Jae Ho Jeong, Jaekyung Cheon, Jin Won Kim, Jina Yun, Sun Min Lim, Yongjun Cha, Se
    Cancer Research and Treatment.2022; 54(1): 1.     CrossRef
  • State legislative trends related to biomarker testing
    Gelareh Sadigh, Hilary Gee Goeckner, Ella A. Kazerooni, Bruce E. Johnson, Robert A. Smith, Devon V. Adams, Ruth C. Carlos
    Cancer.2022; 128(15): 2865.     CrossRef
  • Clinical Application of Next-Generation Sequencing in Patients With Breast Cancer: Real-World Data
    Koung Jin Suh, Se Hyun Kim, Yu Jung Kim, Heechul Shin, Eunyoung Kang, Eun-Kyu Kim, Sejoon Lee, Ji Won Woo, Hee Young Na, Soomin Ahn, Bum-Sup Jang, In Ah Kim, So Yeon Park, Jee Hyun Kim
    Journal of Breast Cancer.2022; 25(5): 366.     CrossRef
  • Small-Cell Lung Cancer: Is the Black Box Finally Opening Up?
    Birgitta I. Hiddinga, Klaas Kok
    Cancers.2021; 13(2): 236.     CrossRef
  • Real‐world utility of next‐generation sequencing for targeted gene analysis and its application to treatment in lung adenocarcinoma
    Jwa Hoon Kim, Shinkyo Yoon, Dae Ho Lee, Se Jin Jang, Sung‐Min Chun, Sang‐We Kim
    Cancer Medicine.2021; 10(10): 3197.     CrossRef
  • Actionability evaluation of biliary tract cancer by genome transcriptome analysis and Asian cancer knowledgebase
    Yuki Okawa, Nobutaka Ebata, Nayoung K.D. Kim, Masashi Fujita, Kazuhiro Maejima, Shota Sasagawa, Toru Nakamura, Woong-Yang Park, Satoshi Hirano, Hidewaki Nakagawa
    Oncotarget.2021; 12(15): 1540.     CrossRef
  • Development and Validation of Targeted Gene Sequencing Panel Based Companion Diagnostic for Korean Patients with Solid Tumors
    Byung-Joo Min, Woo Seung Lee, Myung-Eui Seo, Kye-Hwa Lee, Seung-Yong Jeong, Ja-Lok Ku, Yeul Hong Kim, Sang-Won Shin, Ju Han Kim
    Cancers.2021; 13(20): 5112.     CrossRef
  • Junction Location Identifier (JuLI)
    Hyun-Tae Shin, Nayoung K.D. Kim, Jae Won Yun, Boram Lee, Sungkyu Kyung, Ki-Wook Lee, Daeun Ryu, Jinho Kim, Joon Seol Bae, Donghyun Park, Yoon-La Choi, Se-Hoon Lee, Myung-Ju Ahn, Keunchil Park, Woong-Yang Park
    The Journal of Molecular Diagnostics.2020; 22(3): 304.     CrossRef
  • Simple prediction model for homologous recombination deficiency in breast cancers in adolescents and young adults
    Tomoko Watanabe, Takayuki Honda, Hirohiko Totsuka, Masayuki Yoshida, Maki Tanioka, Kouya Shiraishi, Yoko Shimada, Eri Arai, Mineko Ushiama, Kenji Tamura, Teruhiko Yoshida, Yae Kanai, Takashi Kohno
    Breast Cancer Research and Treatment.2020; 182(2): 491.     CrossRef
  • 15,017 View
  • 469 Download
  • 15 Web of Science
  • 14 Crossref
Close layer
Phase 1 Studies of Poziotinib, an Irreversible Pan-HER Tyrosine Kinase Inhibitor in Patients with Advanced Solid Tumors
Tae Min Kim, Keun-Wook Lee, Do-Youn Oh, Jong-Seok Lee, Seock-Ah Im, Dong-Wan Kim, Sae-Won Han, Yu Jung Kim, Tae-You Kim, Jee Hyun Kim, Hyesun Han, Woo Ho Kim, Yung-Jue Bang
Cancer Res Treat. 2018;50(3):835-842.   Published online August 29, 2017
DOI: https://doi.org/10.4143/crt.2017.303
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Poziotinib, a pan-human epidermal growth factor receptor 2 (HER) tyrosine kinase inhibitor, has shown potent activity againstwild type of epidermal growth factorreceptor(EGFR) family kinases including EGFR, HER2, and HER4 and EGFR-mutant cells in vitro. Two phase I studies were conducted to determine the maximum tolerated dose (MTD), pharmacokinetics, safety, and antitumor activity against advanced solid tumors.
Materials and Methods
Standard 3+3 dose escalation scheme using two different dosing schedules were studied: once daily, 14-day on, and 7-day off (intermittent schedule); and once daily continuous dosing with food effect. Additional patients were enrolled in an expansion cohort.
Results
A total of 75 patients were enrolled in the two studies. The most common drug-related treatment-emergent adverse eventswere diarrhea,rash, stomatitis, pruritus, and anorexia. Doselimiting toxicities were grade 3 diarrhea in the intermittent schedule and grade 3 anorexia and diarrhea in the continuous dosing schedule. The MTDs were determined as 24 mg/day in the intermittent dosing schedule and 18 mg/day in the continuous dosing schedule. Eight (16%) and 24 (47%) of 51 evaluable patients in the intermittent schedule achieved partial response (PR) and stable disease (SD), respectively. Four (21%) and six (32%) of 19 evaluable patients in continuous dosing schedule achieved PR and SD, respectively. Patients with PR (n=7) or SD ≥ 12 weeks (n=7) had HER2 amplification (n=7; breast cancer, 5; and stomach cancer, 2) and EGFR amplification (n=1, squamous cell lung cancer).
Conclusion
Poziotinib was safe and well tolerated in patients with advanced solid tumors. It showed an encouraging activity against EGFR-mutant and HER2-amplified cancers.

Citations

Citations to this article as recorded by  
  • The continually evolving landscape of novel therapies in oncogene-driven advanced non-small-cell lung cancer
    Barbara Melosky, Rosalyn A. Juergens, Shantanu Banerji, Adrian Sacher, Paul Wheatley-Price, Stephanie Snow, Ming-Sound Tsao, Natasha B. Leighl, Ilidio Martins, Parneet Cheema, Geoffrey Liu, Quincy S. C. Chu
    Therapeutic Advances in Medical Oncology.2025;[Epub]     CrossRef
  • Cellular polarity pilots breast cancer progression and immunosuppression
    Jie Huang, Shufeng Luo, Juan Shen, Maya Lee, Rachel Chen, Shenglin Ma, Lun-Quan Sun, Jian Jian Li
    Oncogene.2025; 44(12): 783.     CrossRef
  • The Brain-Penetrant Pan-ErbB Inhibitor Poziotinib Effectively Targets HER2+ Breast Cancer Brain Metastases
    Danyyl Ippolitov, Yi-Han Lin, Jeremy Spence, Aleksandra Glogowska, Thatchawan Thanasupawat, Jason Beiko, Marc R. Del Bigio, Xin Xu, Amy Q. Wang, Darian Williams, Raul Calvo, Abhijeet Kapoor, Juan J. Marugan, Mark J. Henderson, Thomas Klonisch, Sabine Homb
    Cancer Research.2025; 85(8): 1514.     CrossRef
  • Secondary Mutations of the EGFR Gene That Confer Resistance to Mobocertinib in EGFR Exon 20 Insertion
    Akira Hamada, Kenichi Suda, Masaya Nishino, Keiko Obata, Hana Oiki, Tomoyo Fukami, Shota Fukuda, Toshio Fujino, Shuta Ohara, Takamasa Koga, Masato Chiba, Masaki Shimoji, Masaoki Ito, Toshiki Takemoto, Junichi Soh, Yasuhiro Tsutani, Tetsuya Mitsudomi
    Journal of Thoracic Oncology.2024; 19(1): 71.     CrossRef
  • Poziotinib treatment in patients with HER2-positive advanced breast cancer who have received prior anti-HER2 regimens
    Azadeh Nasrazadani, Juan Luis Gomez Marti, Kate Lathrop, Alvaro Restrepo, Szu-Yun Leu, Gajanan Bhat, Adam Brufsky
    Breast Cancer Research and Treatment.2024; 205(1): 29.     CrossRef
  • HER2-targeted therapies beyond breast cancer — an update
    Jeesun Yoon, Do-Youn Oh
    Nature Reviews Clinical Oncology.2024; 21(9): 675.     CrossRef
  • Emerging Targeted Therapies for HER2-Positive Breast Cancer
    María Florencia Mercogliano, Sofía Bruni, Florencia Luciana Mauro, Roxana Schillaci
    Cancers.2023; 15(7): 1987.     CrossRef
  • Inhibitory effect of Schisandrin on the pharmacokinetics of poziotinib in vivo and in vitro by UPLC‐MS/MS
    Shuanghu Wang, Mengming Xia, Yu Wang, Zebei Lu, Peiwu Geng, Dapeng Dai, Yunfang Zhou, Qingjun Wu
    Thoracic Cancer.2023; 14(14): 1276.     CrossRef
  • Neratinib for HER2-positive breast cancer with an overlooked option
    Liting Guo, Weiwei Shao, Chenfei Zhou, Hui Yang, Liu Yang, Qu Cai, Junqing Wang, Yan Shi, Lei Huang, Jun Zhang
    Molecular Medicine.2023;[Epub]     CrossRef
  • Clinical Relevance of Patient-Derived Organoid of Surgically Resected Lung Cancer as an In Vitro Model for Biomarker and Drug Testing
    Takamasa Koga, Junichi Soh, Akira Hamada, Yuki Miyano, Toshio Fujino, Keiko Obata, Shuta Ohara, Masaya Nishino, Masato Chiba, Masaki Shimoji, Toshiki Takemoto, Kenichi Suda, Kazuko Sakai, Hidenori Sato, Tetsuya Mitsudomi
    JTO Clinical and Research Reports.2023; 4(9): 100554.     CrossRef
  • Acquired Secondary HER2 Mutations Enhance HER2/MAPK Signaling and Promote Resistance to HER2 Kinase Inhibition in Breast Cancer
    Arnaldo Marín, Abdullah Al Mamun, Hima Patel, Hiroaki Akamatsu, Dan Ye, Dhivya R. Sudhan, Lisa Eli, Katherine Marcelain, Benjamin P. Brown, Jens Meiler, Carlos L. Arteaga, Ariella B. Hanker
    Cancer Research.2023; 83(18): 3145.     CrossRef
  • In Silico and In Vitro Exploration of Poziotinib and Olmutinib Synergy in Lung Cancer: Role of hsa-miR-7-5p in Regulating Apoptotic Pathway Marker Genes
    Salman Alamery, Anfal AlAjmi, Tanveer A. Wani, Seema Zargar
    Medicina.2023; 59(11): 1923.     CrossRef
  • Unlocking New Avenues in Breast Cancer Treatment: The Synergy of Kinase Inhibitors and Immunotherapy
    María José Bravo, Antonio Manuel Burgos-Molina, Marilina García-Aranda, Maximino Redondo, Teresa Téllez
    Cancers.2023; 15(23): 5499.     CrossRef
  • Novel HER-2 Targeted Therapies in Breast Cancer
    Catarina Lopes Fernandes, Diogo J. Silva, Alexandra Mesquita
    Cancers.2023; 16(1): 87.     CrossRef
  • Trastuzumab Deruxtecan for HER2+ Advanced Breast Cancer
    Jiyun Lee, Yeon Hee Park
    Future Oncology.2022; 18(1): 7.     CrossRef
  • Poziotinib in Non–Small-Cell Lung Cancer Harboring HER2 Exon 20 Insertion Mutations After Prior Therapies: ZENITH20-2 Trial
    Xiuning Le, Robin Cornelissen, Marina Garassino, Jeffrey M. Clarke, Nishan Tchekmedyian, Jonathan W. Goldman, Szu-Yun Leu, Gajanan Bhat, Francois Lebel, John V. Heymach, Mark A. Socinski
    Journal of Clinical Oncology.2022; 40(7): 710.     CrossRef
  • HER2-Altered Non-Small Cell Lung Cancer: Biology, Clinicopathologic Features, and Emerging Therapies
    Xin Yu, Xianxiu Ji, Chunxia Su
    Frontiers in Oncology.2022;[Epub]     CrossRef
  • Poziotinib for EGFR exon 20-mutant NSCLC: Clinical efficacy, resistance mechanisms, and impact of insertion location on drug sensitivity
    Yasir Y. Elamin, Jacqulyne P. Robichaux, Brett W. Carter, Mehmet Altan, Hai Tran, Don L. Gibbons, Simon Heeke, Frank V. Fossella, Vincent K. Lam, Xiuning Le, Marcelo V. Negrao, Monique B. Nilsson, Anisha Patel, R.S.K. Vijayan, Jason B. Cross, Jianjun Zhan
    Cancer Cell.2022; 40(7): 754.     CrossRef
  • Tailoring antiHer2 treatment strategies in breast cancer and beyond
    Palma Fedele, Valeria Sanna, Anna Natalizia Santoro, Maria Laura Iaia, Alessandro Fancellu
    Current Problems in Cancer.2022; 46(5): 100892.     CrossRef
  • HER2-targeted advanced metastatic gastric/gastroesophageal junction adenocarcinoma: treatment landscape and future perspectives
    Weiling Li, Xiaoling Zhang, Yunyi Du, Ying Zhang, Jing Lu, Wenqing Hu, Jun Zhao
    Biomarker Research.2022;[Epub]     CrossRef
  • Deciphering the Impact of HER2 Alterations on Non-Small-Cell Lung Cancer: From Biological Mechanisms to Therapeutic Approaches
    Christophe Bontoux, Jonathan Benzaquen, Véronique Hofman, Simon Heeke, Paul Hannetel, Pierre Capela-Brosseau-Laborde, Charles-Hugo Marquette, Marius Ilié, Paul Hofman
    Journal of Personalized Medicine.2022; 12(10): 1651.     CrossRef
  • An ultra-performance LC–MS/MS method for determination of JRF103 in human plasma: application in first in-patient study
    Ying Jin, Xiangjie Di, Lisha Fu, Mengyu Zhang, Neng Qiu, Runhan Liu, Fangqun Li, Xiaohui Qi, Xiaoxu Wang, Yongsheng Wang, Zhenlei Wang
    Bioanalysis.2022; 14(17): 1165.     CrossRef
  • Uncommon targets in non-small cell lung cancer: Everyone wants a slice of cake
    Alessandro De Toma, Giuseppe Lo Russo, Diego Signorelli, Filippo Pagani, Giovanni Randon, Giulia Galli, Arsela Prelaj, Roberto Ferrara, Claudia Proto, Monica Ganzinelli, Nicoletta Zilembo, Filippo de Braud, Marina Chiara Garassino
    Critical Reviews in Oncology/Hematology.2021; 160: 103299.     CrossRef
  • Effects of dacomitinib on the pharmacokinetics of poziotinib in vivo and in vitro
    Weiping Ji, Jiquan Shen, Bo Wang, Feifei Chen, Deru Meng, Shuanghu Wang, Dapeng Dai, Yunfang Zhou, Changxiong Wang, Quan Zhou
    Pharmaceutical Biology.2021; 59(1): 455.     CrossRef
  • Treating Advanced Unresectable or Metastatic HER2-Positive Breast Cancer: A Spotlight on Tucatinib
    Lara Ulrich, Alicia FC Okines
    Breast Cancer: Targets and Therapy.2021; Volume 13: 361.     CrossRef
  • Current therapeutic options for gastric adenocarcinoma
    C.R. Akshatha, Smitha Bhat, R. Sindhu, Dharini Shashank, Sarana Rose Sommano, Wanaporn Tapingkae, Ratchadawan Cheewangkoon, Shashanka K. Prasad
    Saudi Journal of Biological Sciences.2021; 28(9): 5371.     CrossRef
  • The rapidly evolving landscape of novel targeted therapies in advanced non-small cell lung cancer
    Barbara Melosky, Paul Wheatley-Price, Rosalyn A. Juergens, Adrian Sacher, Natasha B. Leighl, Ming-Sound Tsao, Parneet Cheema, Stephanie Snow, Geoffrey Liu, Paul B. Card, Quincy Chu
    Lung Cancer.2021; 160: 136.     CrossRef
  • Pathogenesis and Potential Therapeutic Targets for Triple-Negative Breast Cancer
    Chia-Jung Li, Yen-Dun Tony Tzeng, Yi-Han Chiu, Hung-Yu Lin, Ming-Feng Hou, Pei-Yi Chu
    Cancers.2021; 13(12): 2978.     CrossRef
  • Next‐Generation Kinase Inhibitors Targeting Specific Biomarkers in Non‐Small Cell Lung Cancer (NSCLC): A Recent Overview
    Debasis Das, Jingbing Wang, Jian Hong
    ChemMedChem.2021; 16(16): 2459.     CrossRef
  • Discovery of first-in-class imidazothiazole-based potent and selective ErbB4 (HER4) kinase inhibitors
    Seyed-Omar Zaraei, Rawan M. Sbenati, Nour N. Alach, Hanan S. Anbar, Randa El-Gamal, Hamadeh Tarazi, Mahmoud K. Shehata, Mohammed S. Abdel-Maksoud, Chang-Hyun Oh, Mohammed I. El-Gamal
    European Journal of Medicinal Chemistry.2021; 224: 113674.     CrossRef
  • Breast Cancer Treatments: Updates and New Challenges
    Anna Burguin, Caroline Diorio, Francine Durocher
    Journal of Personalized Medicine.2021; 11(8): 808.     CrossRef
  • Targeting HER2 in non-small-cell lung cancer (NSCLC): a glimpse of hope? An updated review on therapeutic strategies in NSCLC harbouring HER2 alterations
    M. Riudavets, I. Sullivan, P. Abdayem, D. Planchard
    ESMO Open.2021; 6(5): 100260.     CrossRef
  • A phase II study of poziotinib in patients with recurrent and/or metastatic head and neck squamous cell carcinoma
    Ji Hyun Lee, Seong Gu Heo, Beung‐Chul Ahn, Min Hee Hong, Byoung Chul Cho, Sun Min Lim, Hye Ryun Kim
    Cancer Medicine.2021; 10(20): 7012.     CrossRef
  • In vitro validation study of HER2 and HER4 mutations identified in an ad hoc secondary analysis of the LUX-Lung 8 randomized clinical trial
    Akira Hamada, Kenichi Suda, Takamasa Koga, Toshio Fujino, Masaya Nishino, Shuta Ohara, Masato Chiba, Masaki Shimoji, Toshiki Takemoto, Junichi Soh, Tetsuro Uchida, Tetsuya Mitsudomi
    Lung Cancer.2021; 162: 79.     CrossRef
  • HER2 Aberrations in Non-Small Cell Lung Cancer: From Pathophysiology to Targeted Therapy
    Ioannis A. Vathiotis, Andriani Charpidou, Niki Gavrielatou, Konstantinos N. Syrigos
    Pharmaceuticals.2021; 14(12): 1300.     CrossRef
  • Conformational Landscapes of HER2 Exon 20 Insertions Explain Their Sensitivity to Kinase Inhibitors in Lung Adenocarcinoma
    Shen Zhao, Wenfeng Fang, Hui Pan, Yunpeng Yang, Ying Liang, Lin Yang, Xiaorong Dong, Jianhua Zhan, Kai Wang, Li Zhang
    Journal of Thoracic Oncology.2020; 15(6): 962.     CrossRef
  • Drug resistance to targeted therapeutic strategies in non-small cell lung cancer
    Wen-juan Liu, Yue Du, Ru Wen, Ming Yang, Jian Xu
    Pharmacology & Therapeutics.2020; 206: 107438.     CrossRef
  • Novel drugs targeting EGFR and HER2 exon 20 mutations in metastatic NSCLC
    Iosune Baraibar, Laura Mezquita, Ignacio Gil-Bazo, David Planchard
    Critical Reviews in Oncology/Hematology.2020; 148: 102906.     CrossRef
  • Mutation Variants and Co-Mutations as Genomic Modifiers of Response to Afatinib in HER2-Mutant Lung Adenocarcinoma
    Wenfeng Fang, Shen Zhao, Ying Liang, Yunpeng Yang, Lin Yang, Xiaorong Dong, Li Zhang, Yong Tang, Shoufeng Wang, Yang Yang, Xiaoyan Ma, Minghui Wang, Wenjing Wang, Songhui Zhao, Kai Wang, Song Gao, Li Zhang
    The Oncologist.2020; 25(3): e545.     CrossRef
  • Clinical Activity of Afatinib in Patients With Non–Small-Cell Lung Cancer Harboring Uncommon EGFR Mutations: A Spanish Retrospective Multicenter Study
    Teresa Moran, Alvaro Taus, Edurne Arriola, Carlos Aguado, Manuel Dómine, Ana Gómez Rueda, Antonio Calles, Susana Cedrés, Nuria Viñolas, Dolores Isla, Ramón Palmero, María Sereno, Victor Diaz, Oscar Juan, Raquel Marsé, Paloma Martín Martorell, José Miguel
    Clinical Lung Cancer.2020; 21(5): 428.     CrossRef
  • HER2-positive advanced breast cancer treatment in 2020
    Marcelle G. Cesca, Lucas Vian, Sofia Cristóvão-Ferreira, Noam Pondé, Evandro de Azambuja
    Cancer Treatment Reviews.2020; 88: 102033.     CrossRef
  • New Therapeutics in HER2-Positive Advanced Breast Cancer: Towards a Change in Clinical Practices?
    Essia Mezni, Cécile Vicier, Mathilde Guerin, Renaud Sabatier, François Bertucci, Anthony Gonçalves
    Cancers.2020; 12(6): 1573.     CrossRef
  • HER2 Exon 20 Insertion Mutations in Lung Adenocarcinoma: Case Series and Response to Pyrotinib
    Xinyong Zhang, Jialin Lv, Yuhua Wu, Na Qin, Li Ma, Xi Li, Jingying Nong, Hui Zhang, Quan Zhang, Xinjie Yang, Huibo Shi, Jinghui Wang, Shucai Zhang
    Frontiers in Oncology.2020;[Epub]     CrossRef
  • Clinical implications of HER2 mRNA expression and intrinsic subtype in refractory HER2-positive metastatic breast cancer treated with pan-HER inhibitor, poziotinib
    Ji-Yeon Kim, Kyunghee Park, Seock-Ah Im, Kyung Hae Jung, Joohyuk Sohn, Keun Seok Lee, Jee Hyun Kim, Yaewon Yang, Yeon Hee Park
    Breast Cancer Research and Treatment.2020; 184(3): 743.     CrossRef
  • EGFR exon 20 insertions in advanced non-small cell lung cancer: A new history begins
    Jordi Remon, Lizza E.L. Hendriks, Andres F. Cardona, Benjamin Besse
    Cancer Treatment Reviews.2020; 90: 102105.     CrossRef
  • Beyond EGFR, ALK and ROS1: Current evidence and future perspectives on newly targetable oncogenic drivers in lung adenocarcinoma
    Giuseppe Lamberti, Elisa Andrini, Monia Sisi, Alessandro Rizzo, Claudia Parisi, Alessandro Di Federico, Francesco Gelsomino, Andrea Ardizzoni
    Critical Reviews in Oncology/Hematology.2020; 156: 103119.     CrossRef
  • Tyrosine Kinase Inhibitors in the Combination Therapy of HER2 Positive Breast Cancer
    Xue Yang, Dapeng Wu, Shengli Yuan
    Technology in Cancer Research & Treatment.2020;[Epub]     CrossRef
  • Poziotinib Inhibits the Efflux Activity of the ABCB1 and ABCG2 Transporters and the Expression of the ABCG2 Transporter Protein in Multidrug Resistant Colon Cancer Cells
    Yongchao Zhang, Zhuo-Xun Wu, Yuqi Yang, Jing-Quan Wang, Jun Li, Zoey Sun, Qiu-Xu Teng, Charles R. Ashby, Dong-Hua Yang
    Cancers.2020; 12(11): 3249.     CrossRef
  • Role of Her-2 in Gastrointestinal Tumours beyond Gastric Cancer: A Tool for Precision Medicine
    Csongor G. Lengyel, Baker Habeeb, Shah Z. Khan, Khalid El Bairi, Sara C. Altuna, Sadaqat Hussain, Syed Ayub Mazher, Dario Trapani, Angelica Petrillo
    Gastrointestinal Disorders.2020; 3(1): 1.     CrossRef
  • Metastatic Breast Cancer Patient With Activating HER2 Exon 20 Insertion Mutation With Response to Poziotinib: Case Report of Compassionate Drug Use
    Apurva Pandey, Adam M. Brufsky
    Clinical Breast Cancer.2019; 19(1): e7.     CrossRef
  • Recent advancements of 4-aminoquinazoline derivatives as kinase inhibitors and their applications in medicinal chemistry
    Debasis Das, Jian Hong
    European Journal of Medicinal Chemistry.2019; 170: 55.     CrossRef
  • Receptor tyrosine kinases in PI3K signaling: The therapeutic targets in cancer
    Wei Jiang, Meiju Ji
    Seminars in Cancer Biology.2019; 59: 3.     CrossRef
  • A phase I/II study of poziotinib combined with paclitaxel and trastuzumab in patients with HER2-positive advanced gastric cancer
    Tae-Yong Kim, Hye Sook Han, Keun-Wook Lee, Dae Young Zang, Sun Young Rha, Young Iee Park, Jin-Soo Kim, Kyung-Hun Lee, Se Hoon Park, Eun-Kee Song, Soo-A Jung, NaMi Lee, Yeul Hong Kim, Jae Yong Cho, Yung-Jue Bang
    Gastric Cancer.2019; 22(6): 1206.     CrossRef
  • Preclinical Characteristics of the Irreversible Pan-HER Kinase Inhibitor Neratinib Compared with Lapatinib: Implications for the Treatment of HER2-Positive and HER2-Mutated Breast Cancer
    Denis M. Collins, Neil T. Conlon, Srinivasaraghavan Kannan, Chandra S. Verma, Lisa D. Eli, Alshad S. Lalani, John Crown
    Cancers.2019; 11(6): 737.     CrossRef
  • Molecular alterations and poziotinib efficacy, a pan‐HER inhibitor, in human epidermal growth factor receptor 2 (HER2)‐positive breast cancers: Combined exploratory biomarker analysis from a phase II clinical trial of poziotinib for refractory HER2‐positi
    Ji‐Yeon Kim, Eunjin Lee, Kyunghee Park, Hae Hyun Jung, Woong‐Yang Park, Kyung‐Hun Lee, Joohyuk Sohn, Keun Seok Lee, Kyung Hae Jung, Jee Hyun Kim, Ki Hyeong Lee, Seock‐Ah Im, Yeon Hee Park
    International Journal of Cancer.2019; 145(6): 1669.     CrossRef
  • Emergence of ERBB2 Mutation as a Biomarker and an Actionable Target in Solid Cancers
    Janakiraman Subramanian, Archana Katta, Ashiq Masood, Dashavantha Reddy Vudem, Rama Krishna Kancha
    The Oncologist.2019; 24(12): e1303.     CrossRef
  • Activity of a novel HER2 inhibitor, poziotinib, for HER2 exon 20 mutations in lung cancer and mechanism of acquired resistance: An in vitro study
    Takamasa Koga, Yoshihisa Kobayashi, Kenji Tomizawa, Kenichi Suda, Takayuki Kosaka, Yuichi Sesumi, Toshio Fujino, Masaya Nishino, Shuta Ohara, Masato Chiba, Masaki Shimoji, Toshiki Takemoto, Makoto Suzuki, Pasi A. Jänne, Tetsuya Mitsudomi
    Lung Cancer.2018; 126: 72.     CrossRef
  • A phase II trial of the pan‐HER inhibitor poziotinib, in patients with HER2‐positive metastatic breast cancer who had received at least two prior HER2‐directed regimens: results of the NOV120101‐203 trial
    Yeon Hee Park, Kyung‐Hun Lee, Joo Hyuk Sohn, Keun Seok Lee, Kyung Hae Jung, Jee‐Hyun Kim, Ki Hyeong Lee, Jin Seok Ahn, Tae‐Yong Kim, Gun Min Kim, In Hae Park, Sung‐Bae Kim, Se Hyun Kim, Hye Sook Han, Young‐Hyuck Im, Jin‐Hee Ahn, Jung‐Yong Kim, Jahoon Kang
    International Journal of Cancer.2018; 143(12): 3240.     CrossRef
  • EGFR Exon 20 Insertion Mutations Display Sensitivity to Hsp90 Inhibition in Preclinical Models and Lung Adenocarcinomas
    Susan E. Jorge, Antonio R. Lucena-Araujo, Hiroyuki Yasuda, Zofia Piotrowska, Geoffrey R. Oxnard, Deepa Rangachari, Mark S. Huberman, Lecia V. Sequist, Susumu S. Kobayashi, Daniel B. Costa
    Clinical Cancer Research.2018; 24(24): 6548.     CrossRef
  • 13,835 View
  • 689 Download
  • 62 Web of Science
  • 59 Crossref
Close layer
Redefining the Positive Circumferential Resection Margin by Incorporating Preoperative Chemoradiotherapy Treatment Response in Locally Advanced Rectal Cancer: A Multicenter Validation Study
Joo Ho Lee, Eui Kyu Chie, Seung-Yong Jeong, Tae-You Kim, Dae Yong Kim, Tae Hyun Kim, Sun Young Kim, Ji Yeon Baek, Hee Jin Chang, Min Ju Kim, Sung Chan Park, Jae Hwan Oh, Sung Hwan Kim, Jong Hoon Lee, Doo Ho Choi, Hee Chul Park, Sung-Bum Kang, Jae-Sung Kim
Cancer Res Treat. 2018;50(2):506-517.   Published online May 24, 2017
DOI: https://doi.org/10.4143/crt.2016.607
AbstractAbstract PDFPubReaderePub
Purpose
This study was conducted to validate the prognostic influence of treatment response among patients with positive circumferential resection margin for locally advanced rectal cancer.
Materials and Methods
Clinical data of 197 patientswith positive circumferentialresection margin defined as ≤ 2 mm after preoperative chemoradiotherapy followed by total mesorectal excision between 2004 and 2009were collected forthis multicenter validation study. All patients underwent median 50.4Gy radiationwith concurrentfluoropyrimidine based chemotherapy. Treatmentresponse was dichotomized to good response, including treatmentresponse of grade 2 or 3, and poor response, including grade 0 or 1.
Results
After 52 months median follow-up, 5-year overall survival (OS) for good responders and poor responders was 79.1% and 48.4%, respectively (p < 0.001). In multivariate analysis, circumferential resection margin involvement and treatment response were a prognosticator for OS and locoregional recurrence-free survival. In subgroup analysis, good responders with close margin showed significantly better survival outcomes for survival. Good responders with involved margin and poor responders with close margin shared similar results, whereas poorresponderswith involved margin hadworst survival (5-year OS, 81.2%, 57.0%, 50.0%, and 32.4%, respectively; p < 0.001).
Conclusion
Among patients with positive circumferential resection margin after preoperative chemoradiotherapy, survival of the good responders was significantly better than poor responders. Subgroup analysis revealed that definition of positive circumferential resection margin may be individualized as involvement for good responders, whereas ≤ 2 mm for poor responders.

Citations

Citations to this article as recorded by  
  • Tailored Strategy for Locally Advanced Rectal Carcinoma (GRECCAR 4): Long-term Results From a Multicenter, Randomized, Open-Label, Phase II Trial
    Philippe Rouanet, Eric Rullier, Bernard Lelong, Philippe Maingon, Jean-Jacques Tuech, Denis Pezet, Florence Castan, Stephanie Nougaret
    Diseases of the Colon & Rectum.2022; 65(8): 986.     CrossRef
  • Colorectal Cancer Surgery Quality in Manitoba: A Population-Based Descriptive Analysis
    Iresha Ratnayake, Jason Park, Natalie Biswanger, Allison Feely, Grace Musto, Kathleen Decker
    Current Oncology.2021; 28(3): 2239.     CrossRef
  • 11,361 View
  • 266 Download
  • 4 Web of Science
  • 2 Crossref
Close layer
Korean Cancer Patients’ Awareness of Clinical Trials, Perceptions on the Benefit and Willingness to Participate
Yoojoo Lim, Jee Min Lim, Won Jae Jeong, Kyung-Hun Lee, Bhumsuk Keam, Tae-Yong Kim, Tae Min Kim, Sae-Won Han, Do Youn Oh, Dong-Wan Kim, Tae-You Kim, Dae Seog Heo, Yung-Jue Bang, Seock-Ah Im
Cancer Res Treat. 2017;49(4):1033-1043.   Published online April 7, 2017
DOI: https://doi.org/10.4143/crt.2016.413
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study was to assess current levels of awareness of clinical trials (CTs), perceptions regarding their benefits and willingness to participate to CTs among Korean cancer patients.
Materials and Methods
From December 2012 to August 2015, we distributed questionnaires to cancer patients receiving systemic anti-cancer therapy at Seoul National University Hospital, Seoul, Korea.
Results
A total of 397 out of 520 requested patients (76.3%) responded to the survey. Among the 397 patients, 62.5% were female and the median age was 52 years. Overall, 97.4% (387/397) answered that they have at least heard of CTs. When asked about their level of awareness, 23.8% (92/387) answered that they could more than roughly explain about CTs. The average visual analogue scale score of CT benefit in all patients was 6.43 (standard deviation, 2.20). Patients who were only familiar with the term without detailed knowledge of the contents had the least expectation of benefit from CTs (p=0.015). When asked about their willingness to participate in CTs, 56.7% (225/397) answered positively. Patients with higher levels of awareness of CTs showed higher willingness to participate (p < 0.001). Heavily treated patients and patients with previous experience regarding CTs also showed a higher willingness to participate (p < 0.001). The perceived benefit of CTs was higher in the group willing to participate (p=0.026).
Conclusion
The patient’s level of awareness regarding CTs was positively related to the positive perception and willingness to participate. Although the general awareness of CTs was high, a relatively large proportion of patients did not have accurate knowledge; therefore, proper and accurate patient education is necessary.

Citations

Citations to this article as recorded by  
  • Survey of willingness to participate in clinical trials and influencing factors among cancer and non-cancer patients
    Teck Long King, Shirin Hui Tan, Shirley Siang Ning Tan, Wei Hong Lai, Mohamad Adam Bujang, Pei Jye Voon
    Scientific Reports.2025;[Epub]     CrossRef
  • Exploring clinical trials awareness, information access and participation amongst Australians with ovarian cancer: a qualitative study
    Natalie Williams, Hayley Russell, Bridget Bradhurst
    Supportive Care in Cancer.2025;[Epub]     CrossRef
  • Depression and anxiety among hemophilia patients enrolled in clinical trials: a multi-center cohort study
    Zhen Peng, Xiaoyu Zhu, Chongwei Wang, Mingfeng Zhou, Xiaoling Xu, Yin Chen
    Annals of Hematology.2023; 102(7): 1927.     CrossRef
  • Depression and anxiety in cancer patient enrolled in clinical trials with serious adverse events
    Zhen Peng, Chongwei Wang, Yubei Sun, Yan Ma, Jumei Wang, Fei Xu, Xiaoling Xu, Yin Chen
    Cancer Medicine.2023; 12(19): 20015.     CrossRef
  • Acceptance Factors and Psychological Investigation of Clinical Trials in Cancer Patients
    Jiangjie Sun, Jingyi Fang, Chenchen Zhang, Nannan Jia, Weiming Zhao, Jinjian Gao, Yingying Huang, Jiqing Hao, Liping Zhang, Carmen M Galvez-Sánchez
    Behavioural Neurology.2023; 2023: 1.     CrossRef
  • Understanding and attitudes of the Jordanian public about clinical research ethics
    Mera A Ababneh, Sayer I Al-Azzam, Karem Alzoubi, Abeer Rababa’h, Saddam Al Demour
    Research Ethics.2021; 17(2): 228.     CrossRef
  • A patient-focused, theory-guided approach to survey design identified barriers to and drivers of clinical trial participation
    Jamie C. Brehaut, Kelly Carroll, Justin Presseau, Dawn P. Richards, Jenn Gordon, Angèle Bénard, Natasha Hudek, Ian D. Graham, Dean A. Fergusson, Susan Marlin
    Journal of Clinical Epidemiology.2021; 132: 106.     CrossRef
  • Awareness of breast cancer patients in Poland about clinical trials as available treatment options
    Mikołaj Bartoszkiewicz, Joanna Kufel-Grabowska, Maria Litwiniuk
    Breast Disease.2021; 40(1): 33.     CrossRef
  • Results from a Theory-Guided Survey to Support Breast Cancer Trial Participation: Barriers, Enablers, and What to Do about them
    Jamie C. Brehaut, Kelly Carroll, Jenn Gordon, Justin Presseau, Dawn P. Richards, Dean A. Fergusson, Ian D. Graham, Susan Marlin
    Current Oncology.2021; 28(3): 2014.     CrossRef
  • Regional Differences in Access to Clinical Trials for Cancer in Korea
    Woorim Kim, Seongkyeong Jang, Yoon Jung Chang
    Quality Improvement in Health Care.2021; 27(1): 20.     CrossRef
  • How Cancer Patients Perceive Clinical Trials (CTs) in the Era of CTs: Current Perception and Its Differences Between Common and Rare Cancers
    Ji Hyun Park, Ji Sung Lee, HaYeong Koo, Jeong Eun Kim, Jin-Hee Ahn, Min-Hee Ryu, Sook-ryun Park, Shin-kyo Yoon, Jae Cheol Lee, Yong-Sang Hong, Sun Young Kim, Kyo-Pyo Kim, Chang-Hoon Yoo, Jung Yong Hong, Jae Lyun Lee, Kyung Hae Jung, Baek-Yeol Rhyoo, Tae W
    Journal of Cancer Education.2020; 35(3): 545.     CrossRef
  • Colorectal cancer survivors’ willingness to participate in a hypothetical clinical trial of Korean medicine: A cross-sectional study
    Yown Hwangbo, Gyung Mo Son, Kyung Hee Kim, Myeong Sook Kwon, Kun Hyung Kim
    European Journal of Integrative Medicine.2020; 33: 101033.     CrossRef
  • Perception and Satisfaction of Anticancer Drug Clinical Trials in Cancer Patients
    Ju Kyung Jeon, Jeong Hye Kim
    Asian Oncology Nursing.2019; 19(1): 18.     CrossRef
  • Challenges in informed consent decision-making in Korean clinical research: A participant perspective
    Im-Soon Choi, Eun Young Choi, Iyn-Hyang Lee, Dermot Cox
    PLOS ONE.2019; 14(5): e0216889.     CrossRef
  • Clinical Trials: What, Where, When?
    Olga S. Kobyakova, Ivan A. Deev, Evgeny S. Kulikov, Roman I. Shtykh, Igor D. Pimenov, Olga I. Zvonareva, Igor V. Mareev
    Annals of the Russian academy of medical sciences.2018; 73(5): 314.     CrossRef
  • 8,772 View
  • 183 Download
  • 13 Web of Science
  • 15 Crossref
Close layer
Identification of Diverse Adenosine-to-Inosine RNA Editing Subtypes in Colorectal Cancer
Si-Hyun Lee, Hwang-Phill Kim, Jun-Kyu Kang, Sang-Hyun Song, Sae-Won Han, Tae-You Kim
Cancer Res Treat. 2017;49(4):1077-1087.   Published online January 25, 2017
DOI: https://doi.org/10.4143/crt.2016.301
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
RNA editing generates protein diversity by altering RNA sequences in coding regions without changing the overall DNA sequence. Adenosine-to-inosine (A-to-I) RNA editing events have recently been reported in some types of cancer, but they are rare in human colorectal cancer (CRC). Therefore, this study was conducted to identify diverse RNA editing in CRC.
Materials and Methods
We compared transcriptome data of 39 CRC samples and paired adjacent tissues from The Cancer Genome Atlas database to identify RNA editing patterns in CRC, focusing on canonical A-to-I RNA edits in coding sequence regions. We investigated nonsynonymous RNA editing patterns by comparing tumor and normal tissue transcriptome data.
Results
The number of RNA edits varied from 12 to 42 per sample. We also observed that hypoand hyper-RNA editing patterns were distinguishable within the samples. We found 10 recurrent nonsynonymous RNA editing candidates in nine genes (PDLIM, NEIL1, SRP9, GLI1, APMAP, IGFBP7, ZNF358, COPA, and ZNF587B) and validated some by Sanger sequencing and the inosine chemical erasing assay. We further showed that editing at these positions was performed by the adenosine deaminase acting on RNA 1 enzyme. Most of these genes are hypoedited in CRC, but editing of GLI1 was increased in cancer tissues compared with normal tissues.
Conclusion
Our results show that nonsynonymous RNA editing patterns can be used to identify CRC patients and could serve as novel biomarkers for CRC.

Citations

Citations to this article as recorded by  
  • Advances in Detection Methods for A‐to‐I RNA Editing
    Yuxi Yang, Masayuki Sakurai
    WIREs RNA.2025;[Epub]     CrossRef
  • ADAR-mediated RNA editing regulates PVR immune checkpoint in colorectal cancer
    Cheng-Jia Qian, Yu-Shan He, Tao Guo, Ji Tao, Zhi-Yuan Wei, Jia-Li Zhang, Chuanqing Bao, Jian-Huan Chen
    Biochemical and Biophysical Research Communications.2024; 695: 149373.     CrossRef
  • Screening and identification of serum exosomal protein ZNF587B in liquid biopsy for ovarian cancer diagnosis
    Hu Li
    American Journal of Cancer Research.2024; 14(4): 1904.     CrossRef
  • COPA A-to-I RNA editing hijacks endoplasmic reticulum stress to promote metastasis in colorectal cancer
    Shu-yang Wang, Ling-jie Zhang, Guo-jun Chen, Qi-qi Ni, Yuan Huang, Dan Zhang, Fang-yi Han, Wen-feng He, Li-ling He, Yan-qing Ding, Hong-li Jiao, Ya-ping Ye
    Cancer Letters.2023; 553: 215995.     CrossRef
  • The Interplay between RNA Editing Regulator ADAR1 and Immune Environment in Colorectal Cancer
    Guo-Liang Zheng, Guo-Jun Zhang, Yan Zhao, Zhi-Chao Zheng, Xueliang Wu
    Journal of Oncology.2023; 2023: 1.     CrossRef
  • Signal Recognition Particle in Human Diseases
    Morgana K. Kellogg, Elena B. Tikhonova, Andrey L. Karamyshev
    Frontiers in Genetics.2022;[Epub]     CrossRef
  • Differential Transcriptomic Profiles Following Stimulation with Lipopolysaccharide in Intestinal Organoids from Dogs with Inflammatory Bowel Disease and Intestinal Mast Cell Tumor
    Dipak Kumar Sahoo, Dana C. Borcherding, Lawrance Chandra, Albert E. Jergens, Todd Atherly, Agnes Bourgois-Mochel, N. Matthew Ellinwood, Elizabeth Snella, Andrew J. Severin, Martin Martin, Karin Allenspach, Jonathan P. Mochel
    Cancers.2022; 14(14): 3525.     CrossRef
  • Targeting the regulation of aberrant protein production pathway in gastrointestinal cancer treatment
    Hiromichi Sato, Kazuki Sasaki, Tomoaki Hara, Shogo Kobayashi, Yuichiro Doki, Hidetoshi Eguchi, Taroh Satoh, Hideshi Ishii
    Frontiers in Oncology.2022;[Epub]     CrossRef
  • A signal recognition particle-related joint model of LASSO regression, SVM-RFE and artificial neural network for the diagnosis of systemic sclerosis-associated pulmonary hypertension
    Jingxi Xu, Chaoyang Liang, Jiangtao Li
    Frontiers in Genetics.2022;[Epub]     CrossRef
  • Establishment and validation of an RNA binding protein-associated prognostic model for ovarian cancer
    Chaofan He, Fuxin Huang, Kejia Zhang, Jun Wei, Ke Hu, Meng Liang
    Journal of Ovarian Research.2021;[Epub]     CrossRef
  • The Emerging Impact of RNA Editing in Tumor Growth and Metastasis
    Mehrdad Nasrollahzadehsabet, Javad Behroozi
    Annals of Military and Health Sciences Research.2021;[Epub]     CrossRef
  • Noncanonical Functions and Cellular Dynamics of the Mammalian Signal Recognition Particle Components
    Camilla Faoro, Sandro F. Ataide
    Frontiers in Molecular Biosciences.2021;[Epub]     CrossRef
  • Metabolomic Detection Between Pancreatic Cancer and Liver Metastasis Nude Mouse Models Constructed by Using the PANC1-KAI1/CD82 Cell Line
    Shuo Wang, Jiang Chen, Hongyu Li, Xingshun Qi, Xu Liu, Xiaozhong Guo
    Technology in Cancer Research & Treatment.2021;[Epub]     CrossRef
  • Conservation of A-to-I RNA editing in bowhead whale and pig
    Knud Larsen, Mads Peter Heide-Jørgensen, Alexander F. Palazzo
    PLOS ONE.2021; 16(12): e0260081.     CrossRef
  • Quantifying RNA Editing in Deep Transcriptome Datasets
    Claudio Lo Giudice, Domenico Alessandro Silvestris, Shalom Hillel Roth, Eli Eisenberg, Graziano Pesole, Angela Gallo, Ernesto Picardi
    Frontiers in Genetics.2020;[Epub]     CrossRef
  • The Novel Zinc Finger Protein 587B Gene, ZNF587B, Regulates Cell Proliferation and Metastasis in Ovarian Cancer Cells in vivo and in vitro


    Yujie Liu, Qianying Ouyang, Zeen Sun, Jieqiong Tan, Weihua Huang, Jie Liu, Zhaoqian Liu, Honghao Zhou, Feiyue Zeng, Yingzi Liu
    Cancer Management and Research.2020; Volume 12: 5119.     CrossRef
  • Non-Coding RNA Editing in Cancer Pathogenesis
    Giulia Romano, Michela Saviana, Patricia Le, Howard Li, Lavender Micalo, Giovanni Nigita, Mario Acunzo, Patrick Nana-Sinkam
    Cancers.2020; 12(7): 1845.     CrossRef
  • Automated Isoform Diversity Detector (AIDD): a pipeline for investigating transcriptome diversity of RNA-seq data
    Noel-Marie Plonski, Emily Johnson, Madeline Frederick, Heather Mercer, Gail Fraizer, Richard Meindl, Gemma Casadesus, Helen Piontkivska
    BMC Bioinformatics.2020;[Epub]     CrossRef
  • RNA editing alterations define manifestation of prion diseases
    Eirini Kanata, Franc Llorens, Dimitra Dafou, Athanasios Dimitriadis, Katrin Thüne, Konstantinos Xanthopoulos, Nikolaos Bekas, Juan Carlos Espinosa, Matthias Schmitz, Alba Marín-Moreno, Vincenzo Capece, Orr Shormoni, Olivier Andréoletti, Stefan Bonn, Juan
    Proceedings of the National Academy of Sciences.2019; 116(39): 19727.     CrossRef
  • Epigenetic and epitranscriptomic changes in colorectal cancer: diagnostic, prognostic, and treatment implications
    Elisa Porcellini, Noemi Laprovitera, Mattia Riefolo, Matteo Ravaioli, Ingrid Garajova, Manuela Ferracin
    Cancer Letters.2018;[Epub]     CrossRef
  • Aberrant hyperediting of the myeloma transcriptome by ADAR1 confers oncogenicity and is a marker of poor prognosis
    Phaik Ju Teoh, Omer An, Tae-Hoon Chung, Jing Yuan Chooi, Sabrina H. M. Toh, Shuangyi Fan, Wilson Wang, Bryan T. H. Koh, Melissa J. Fullwood, Melissa G. Ooi, Sanjay de Mel, Cinnie Y. Soekojo, Leilei Chen, Siok Bian Ng, Henry Yang, Wee Joo Chng
    Blood.2018; 132(12): 1304.     CrossRef
  • ADAR1 prevents small intestinal injury from inflammation in a murine model of sepsis
    Shanshou Liu, Jiangang Xie, Bin Zhao, Xiaomin Hu, Xiao Li, Bin Zhang, Xianqi Wang, Yanjun Wang, Jinquan Jiang, Wen Yin, Junjie Li
    Cytokine.2018; 104: 30.     CrossRef
  • 11,352 View
  • 424 Download
  • 20 Web of Science
  • 22 Crossref
Close layer
CA19-9 or CEA Decline after the First Cycle of Treatment Predicts Survival in Advanced Biliary Tract Cancer Patients Treated with S-1 and Cisplatin Chemotherapy
Dae-Won Lee, Seock-Ah Im, Yu Jung Kim, Yaewon Yang, Jiyoung Rhee, Im Il Na, Kyung-Hun Lee, Tae-Yong Kim, Sae-Won Han, In Sil Choi, Do-Youn Oh, Jee Hyun Kim, Tae-You Kim, Yung-Jue Bang
Cancer Res Treat. 2017;49(3):807-815.   Published online January 18, 2017
DOI: https://doi.org/10.4143/crt.2016.326
AbstractAbstract PDFPubReaderePub
Purpose
While tumor markers (carbohydrate antigen 19-9 [CA 19-9] and carcinoembryonic antigen [CEA]) can aid in the diagnosis of biliary tract cancer, their prognostic role has not been clearly elucidated. Therefore, this study was conducted to evaluate the prognostic role of tumor markers and tumor marker change in patients with advanced biliary tract cancer.
Materials and Methods
Patients with pathologically proven metastatic or relapsed biliary tract cancer who were treated in a phase II trial of first-line S-1 and cisplatin chemotherapy were enrolled. Serum tumor markers were measured at baseline and after the first cycle of chemotherapy.
Results
Among a total of 104 patients, 80 (77%) had elevated baseline tumor markers (69 with CA 19-9 elevation and 40 with CEA). A decline ≥ 30% of the elevated tumor marker level after the first cycle of chemotherapy conferred an improved time to progression (TTP), overall survival (OS), and better chemotherapy response. Multivariate analysis revealed tumor marker decline as an independent positive prognostic factor of TTP (adjusted hazard ratio [HR], 0.44; p=0.003) and OS (adjusted HR, 0.37; p < 0.001). Subgroup analysis revealed similar results in each group of patients with CA 19-9 elevation and CEA elevation. In addition, elevated baseline CEA was associated with poor survival in both univariate and multivariate analysis.
Conclusion
Tumor marker decline was associated with improved survival in biliary tract cancer. Measuring tumor marker after the first cycle of chemotherapy can be used as an early assessment of treatment outcome.

Citations

Citations to this article as recorded by  
  • Clinical epidemiology of gallbladder cancer in North-Central India and association of immunological markers, NLR, MLR and PLR in the diagnostic/prognostic prediction of GBC
    Jyotsna Singh, Durgesh Shukla, Sanjiv Gupta, Braj Raj Shrivastav, Pramod Kumar Tiwari
    Cancer Treatment and Research Communications.2021; 28: 100431.     CrossRef
  • Neoadjuvant Intraperitoneal Chemotherapy in Patients with Pseudomyxoma Peritonei—A Novel Treatment Approach
    Aruna Prabhu, Andreas Brandl, Satoshi Wakama, Shouzou Sako, Haruaki Ishibashi, Akiyoshi Mizumoto, Nobuyuki Takao, Kousuke Noguchi, Shunsuke Motoi, Masumi Ichinose, Yang Liu, Yutaka Yonemura
    Cancers.2020; 12(8): 2212.     CrossRef
  • Clinical and Translational Research Challenges in Biliary Tract Cancers
    Angela Lamarca, Melissa Frizziero, Mairéad G. McNamara, Juan W. Valle
    Current Medicinal Chemistry.2020; 27(29): 4756.     CrossRef
  • Therapeutic outcomes and prognostic factors in unresectable gallbladder cancer treated with gemcitabine plus cisplatin
    Min su You, Ji Kon Ryu, Young Hoon Choi, Jin Ho Choi, Gunn Huh, Woo Hyun Paik, Sang Hyub Lee, Yong-Tae Kim
    BMC Cancer.2019;[Epub]     CrossRef
  • Efficacy of interventional therapy and effect on inflammatory factors in patients with gastric cancer after chemotherapy
    Puzhao Wu, Jing Wang
    Oncology Letters.2019;[Epub]     CrossRef
  • CA19-9 kinetics during systemic chemotherapy in patients with advanced or recurrent biliary tract cancer
    Naminatsu Takahara, Yousuke Nakai, Hiroyuki Isayama, Takashi Sasaki, Kei Saito, Kensaku Noguchi, Tatsunori Suzuki, Tomoka Nakamura, Tatsuya Sato, Kazunaga Ishigaki, Ryunosuke Hakuta, Tsuyoshi Takeda, Rie Uchino, Suguru Mizuno, Hirofumi Kogure, Minoru Tada
    Cancer Chemotherapy and Pharmacology.2017; 80(6): 1105.     CrossRef
  • 13,163 View
  • 203 Download
  • 7 Web of Science
  • 6 Crossref
Close layer
Antitumor Effect of KX-01 through Inhibiting Src Family Kinases and Mitosis
Seongyeong Kim, Ahrum Min, Kyung-Hun Lee, Yaewon Yang, Tae-Yong Kim, Jee Min Lim, So Jung Park, Hyun-Jin Nam, Jung Eun Kim, Sang-Hyun Song, Sae-Won Han, Do-Youn Oh, Jee Hyun Kim, Tae-You Kim, David Hangauer, Johnson Yiu-Nam Lau, Kyongok Im, Dong Soon Lee, Yung-Jue Bang, Seock-Ah Im
Cancer Res Treat. 2017;49(3):643-655.   Published online October 6, 2016
DOI: https://doi.org/10.4143/crt.2016.168
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
KX-01 is a novel dual inhibitor of Src and tubulin. Unlike previous Src inhibitors that failed to show clinical benefit during treatment of breast cancer, KX-01 can potentially overcome the therapeutic limitations of current Src inhibitors through inhibition of both Src and tubulin. The present study further evaluates the activity and mechanism of KX-01 in vitro and in vivo.
Materials and Methods
The antitumor effect of KX-01 in triple negative breast cancer (TNBC) cell lines was determined by MTT assay. Wound healing and immunofluorescence assays were performed to evaluate the action mechanisms of KX-01. Changes in the cell cycle and molecular changes induced by KX-01 were also evaluated. A MDA-MB-231 mouse xenograft model was used to demonstrate the in vivo effects.
Results
KX-01 effectively inhibited the growth of breast cancer cell lines. The expression of phospho- Src and proliferative-signaling molecules were down-regulated in KX-01–sensitive TNBC cell lines. In addition, migration inhibition was observed by wound healing assay. KX-01– induced G2/M cell cycle arrest and increased the aneuploid cell population in KX-01–sensitive cell lines. Multi-nucleated cells were significantly increased after KX-01 treatment. Furthermore, KX-01 effectively delayed tumor growth in a MDA-MB-231 mouse xenograft model.
Conclusion
KX-01 effectively inhibited cell growth and migration of TNBC cells. Moreover, this study demonstrated that KX-01 showed antitumor effects through the inhibition of Src signaling and the induction of mitotic catastrophe. The antitumor effects of KX-01 were also demonstrated in vivo using a mouse xenograft model.

Citations

Citations to this article as recorded by  
  • Clinical and experimental aspects of tirbanibulin treatments
    Annabel Shen, Rebecca A. Simonette, Peter L. Rady, Stephen K. Tyring
    Archives of Dermatological Research.2025;[Epub]     CrossRef
  • The Potential Strategies for Overcoming Multidrug Resistance and Reducing Side Effects of Monomer Tubulin Inhibitors for Cancer Therapy
    Yingjie Cui, Jing Zhang, Guifang Zhang
    Current Medicinal Chemistry.2024; 31(14): 1874.     CrossRef
  • Efficacy and tolerability of tirbanibulin 1% ointment in the treatment of cancerization field: a real‐life Italian multicenter observational study of 250 patients
    Gianluca Nazzaro, Andrea Carugno, Paolo Bortoluzzi, Stefano Buffon, Chiara Astrua, Elena Zappia, Emanuele Trovato, Stefano Caccavale, Vincenzo Pellegrino, Giovanni Paolino, Riccardo Balestri, Rossella Lacava, Giulia Ciccarese, Alice Verdelli, Stefania Bar
    International Journal of Dermatology.2024; 63(11): 1566.     CrossRef
  • Dickkopf-1 (DKK1) drives growth and metastases in castration-resistant prostate cancer
    Letizia Rinella, Gloria Fiorentino, Mara Compagno, Cristina Grange, Massimo Cedrino, Francesca Marano, Ornella Bosco, Elena Vissio, Luisa Delsedime, Patrizia D’Amelio, Benedetta Bussolati, Emanuela Arvat, Maria Graziella Catalano
    Cancer Gene Therapy.2024; 31(8): 1266.     CrossRef
  • Anti-tumor effects of tirbanibulin in squamous cell carcinoma cells are mediated via disruption of tubulin-polymerization
    Viola K. DeTemple, Antje Walter, Sabine Bredemeier, Ralf Gutzmer, Katrin Schaper-Gerhardt
    Archives of Dermatological Research.2024;[Epub]     CrossRef
  • Tirbanibulin decreases cell proliferation and downregulates protein expression of oncogenic pathways in human papillomavirus containing HeLa cells
    Stephen Moore, Veda Kulkarni, Angela Moore, Jennifer R. Landes, Rebecca Simonette, Qin He, Peter L. Rady, Stephen K. Tyring
    Archives of Dermatological Research.2024;[Epub]     CrossRef
  • Topical Pharmacological Treatment of Actinic Keratoses: Focus on Tirbanibulin 1% Ointment
    Mario Valenti, Matteo Bianco, Alessandra Narcisi, Antonio Costanzo, Riccardo Borroni, Marco Ardigò
    Dermatology Practical & Conceptual.2024; 14(S1): e2024145S.     CrossRef
  • Recent advancement in developing small molecular inhibitors targeting key kinase pathways against triple-negative breast cancer
    Rajibul Islam, Khor Poh Yen, Nur Najihah ’Izzati Mat Rani, Md. Selim Hossain
    Bioorganic & Medicinal Chemistry.2024; 112: 117877.     CrossRef
  • Real-world experience with histological confirmation of clinical response of squamous cell carcinoma to topical tirbanibulin
    Angela Moore, Kara Hurley, Stephen A. Moore, Luke Moore
    JAAD Case Reports.2023; 40: 141.     CrossRef
  • Synthesis and evaluation of tirbanibulin derivatives: a detailed exploration of the structure–activity relationship for anticancer activity
    Jaebeom Park, Minji Kang, Ahyoung Lim, Kyung-Jin Cho, Chong Hak Chae, Byumseok Koh, Hongjun Jeon
    RSC Advances.2023; 13(50): 35583.     CrossRef
  • Tirbanibulina: revisión de su mecanismo de acción novedoso y de cómo encaja en el tratamiento de la queratosis actínica
    Y. Gilaberte, M.T. Fernández-Figueras
    Actas Dermo-Sifiliográficas.2022; 113(1): 58.     CrossRef
  • Insights on Cancer Cell Inhibition, Subcellular Activities, and Kinase Profile of Phenylacetamides Pending 1H-Imidazol-5-One Variants
    Maan T. Khayat, Abdelsattar M. Omar, Farid Ahmed, Mohammad I. Khan, Sara M. Ibrahim, Yosra A. Muhammad, Azizah M. Malebari, Thikryat Neamatallah, Moustafa E. El-Araby
    Frontiers in Pharmacology.2022;[Epub]     CrossRef
  • Identification of New Vulnerabilities in Conjunctival Melanoma Using Image-Based High Content Drug Screening
    Katya Nardou, Michael Nicolas, Fabien Kuttler, Katarina Cisarova, Elifnaz Celik, Mathieu Quinodoz, Nicolo Riggi, Olivier Michielin, Carlo Rivolta, Gerardo Turcatti, Alexandre Pierre Moulin
    Cancers.2022; 14(6): 1575.     CrossRef
  • Targeting regulated cell death (RCD) with small-molecule compounds in triple-negative breast cancer: a revisited perspective from molecular mechanisms to targeted therapies
    Minru Liao, Rui Qin, Wei Huang, Hong-Ping Zhu, Fu Peng, Bo Han, Bo Liu
    Journal of Hematology & Oncology.2022;[Epub]     CrossRef
  • SAR Probing of KX2-391 Provided Analogues With Juxtaposed Activity Profile Against Major Oncogenic Kinases
    Abdelsattar M. Omar, Maan T. Khayat, Farid Ahmed, Yosra A. Muhammad, Azizah M. Malebari, Sara M. Ibrahim, Mohammad I. Khan, Dhaval K. Shah, Wayne E. Childers, Moustafa E. El-Araby
    Frontiers in Oncology.2022;[Epub]     CrossRef
  • Topical Tirbanibulin, a Dual Src Kinase and Tubulin Polymerization Inhibitor, for the Treatment of Plaque-Type Psoriasis: Phase I Results
    Jin-Bon Hong, Po-Yuan Wu, Albert Qin, Yi-Wen Huang, Kuan-Chiao Tseng, Ching-Yu Lai, Wing-Kai Chan, Jane Fang, David L. Cutler, Tsen-Fang Tsai
    Pharmaceutics.2022; 14(10): 2159.     CrossRef
  • Tirbanibulin for Actinic Keratosis: Insights into the Mechanism of Action
    Todd Schlesinger, Eggert Stockfleth, Ayman Grada, Brian Berman
    Clinical, Cosmetic and Investigational Dermatology.2022; Volume 15: 2495.     CrossRef
  • Dual Kinase Targeting in Leukemia
    Luca Mologni, Giovanni Marzaro, Sara Redaelli, Alfonso Zambon
    Cancers.2021; 13(1): 119.     CrossRef
  • Recent Progress on Tubulin Inhibitors with Dual Targeting Capabilities for Cancer Therapy
    Wen Shuai, Guan Wang, Yiwen Zhang, Faqian Bu, Sicheng Zhang, Duane D. Miller, Wei Li, Liang Ouyang, Yuxi Wang
    Journal of Medicinal Chemistry.2021; 64(12): 7963.     CrossRef
  • New FDA oncology small molecule drugs approvals in 2020: Mechanism of action and clinical applications
    Thais Cristina Mendonça Nogueira, Marcus Vinicius Nora de Souza
    Bioorganic & Medicinal Chemistry.2021; 46: 116340.     CrossRef
  • Tirbanibulin: review of its novel mechanism of action and how it fits into the treatment of actinic keratosis
    Y. Gilaberte, M.T. Fernández-Figueras
    Actas Dermo-Sifiliográficas (English Edition).2021;[Epub]     CrossRef
  • Recent progress in small molecule agents for the targeted therapy of triple-negative breast cancer
    Rajibul Islam, Kok Wai Lam
    European Journal of Medicinal Chemistry.2020; 207: 112812.     CrossRef
  • Current advances of tubulin inhibitors as dual acting small molecules for cancer therapy
    Kinsie E Arnst, Souvik Banerjee, Hao Chen, Shanshan Deng, Dong‐Jin Hwang, Wei Li, Duane D Miller
    Medicinal Research Reviews.2019; 39(4): 1398.     CrossRef
  • Reversible binding of the anticancer drug KXO1 (tirbanibulin) to the colchicine-binding site of β-tubulin explains KXO1's low clinical toxicity
    Lu Niu, Jianhong Yang, Wei Yan, Yamei Yu, Yunhua Zheng, Haoyu Ye, Qiang Chen, Lijuan Chen
    Journal of Biological Chemistry.2019; 294(48): 18099.     CrossRef
  • Discovery of Novel Dual Mechanism of Action Src Signaling and Tubulin Polymerization Inhibitors (KX2-391 and KX2-361)
    Michael P. Smolinski, Yahao Bu, James Clements, Irwin H. Gelman, Taher Hegab, David L. Cutler, Jane W. S. Fang, Gerald Fetterly, Rudolf Kwan, Allen Barnett, Johnson Y. N. Lau, David G. Hangauer
    Journal of Medicinal Chemistry.2018; 61(11): 4704.     CrossRef
  • KX2-361: a novel orally bioavailable small molecule dual Src/tubulin inhibitor that provides long term survival in a murine model of glioblastoma
    Michael J. Ciesielski, Yahao Bu, Stephan A. Munich, Paola Teegarden, Michael P. Smolinski, James L. Clements, Johnson Y. N. Lau, David G. Hangauer, Robert A. Fenstermaker
    Journal of Neuro-Oncology.2018; 140(3): 519.     CrossRef
  • 15,384 View
  • 385 Download
  • 24 Web of Science
  • 26 Crossref
Close layer
Efficacy of Letrozole as First-Line Treatment of Postmenopausal Women with Hormone Receptor–Positive Metastatic Breast Cancer in Korea
Seung Hoon Beom, Jisu Oh, Tae-Yong Kim, Kyung-Hun Lee, Yaewon Yang, Koung Jin Suh, Hyeong-Gon Moon, Sae-Won Han, Do-Youn Oh, Wonshik Han, Tae-You Kim, Dong-Young Noh, Seock-Ah Im
Cancer Res Treat. 2017;49(2):454-463.   Published online August 23, 2016
DOI: https://doi.org/10.4143/crt.2016.259
AbstractAbstract PDFPubReaderePub
Purpose
Letrozole showed efficacy and generally favorable toxicities, along with the convenience of oral administration in postmenopausal patients with hormone receptor (HR)–positive metastatic breast cancer (MBC). To the best of our knowledge, there have been no reports of the clinical outcomes in Korean patients, although letrozole is widely used in practice. Therefore, this studywas conducted to affirm the efficacy and toxicities of letrozole in Korean patients.
Materials and Methods
This study retrospectively analyzed 84 HR-positive MBC patients who had been treated with letrozole from January 2001 to December 2012. Clinicopathological characteristics and treatment historywere extracted from medicalrecords. All patients received 2.5 mg letrozole once a day until there were disease progressions or unacceptable toxicity. Progression-free survival (PFS) was the primary endpoint, and secondary endpoints were overall survival (OS), objective response rate (ORR), and toxicity.
Results
The median age of the subjects was 59.3 years. Letrozole treatment resulted in a median PFS of 16.8 months (95% confidence interval [CI], 9.8 to 23.8) and a median OS of 56.4 months (95% CI, 38.1 to 74.7). The ORR was 36.9% for the 84 patients with measurable lesions. Multivariate analysis revealed symptomatic visceral disease (hazard ratio, 3.437; 95% CI, 1.576 to 7.495; p=0.002) and a disease-free interval ≤ 2 years (hazard ratio, 2.697; 95% CI, 1.262 to 5.762; p=0.010) were independently associated with shorter PFS. However, sensitivity to adjuvant hormone treatment was not related to PFS. Letrozole was generally well tolerated.
Conclusion
Letrozole showed considerable efficacy and tolerability as a first-line treatment in postmenopausal patients with HR-positive MBC.

Citations

Citations to this article as recorded by  
  • Is hormonal therapy effective in advanced endometrial cancer? A systematic review and meta-analysis
    Josee-Lyne Ethier, Danielle N. Desautels, Eitan Amir, Helen MacKay
    Gynecologic Oncology.2017; 147(1): 158.     CrossRef
  • 12,870 View
  • 252 Download
  • 1 Web of Science
  • 1 Crossref
Close layer
Splenomegaly and Its Associations with Genetic Polymorphisms and Treatment Outcome in Colorectal Cancer Patients Treated with Adjuvant FOLFOX
Mi-Jung Kim, Sae-Won Han, Dae-Won Lee, Yongjun Cha, Kyung-Hun Lee, Tae-Yong Kim, Do-Youn Oh, Se Hyung Kim, Seock-Ah Im, Yung-Jue Bang, Tae-You Kim
Cancer Res Treat. 2016;48(3):990-997.   Published online January 14, 2016
DOI: https://doi.org/10.4143/crt.2015.296
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Splenomegaly is a clinical surrogate of oxaliplatin-induced sinusoidal obstruction syndrome (SOS). We investigated development of splenomegaly and its association with treatment outcome and genetic polymorphisms following adjuvant 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) in colorectal cancer (CRC) patients.
Materials and Methods
Splenomegaly was determined by spleen volumetry using computed tomography images obtained before initiation of chemotherapy and after completion of adjuvant FOLFOX in CRC patients. Ten genetic polymorphisms in 4 SOS-related genes (VEGFA, MMP9, NOS3, and GSTP1) were analyzed using DNA from peripheral blood mononuclear cells.
Results
Of 124 patients included, increase in spleen size was observed in 109 (87.9%). Median change was 31% (range, –42% to 168%). Patients with splenomegaly had more severe thrombocytopenia compared to patients without splenomegaly during the chemotherapy period (p < 0.0001). The cumulative dose of oxaliplatin and the lowest platelet count during the chemotherapy period were clinical factors associated with splenomegaly. However, no significant associations were found between genetic polymorphisms and development of splenomegaly. Disease-free survival was similar regardless of the development of splenomegaly.
Conclusion
Splenomegaly was frequently observed in patients receiving adjuvant FOLFOX and resulted in more severe thrombocytopenia but did not influence treatment outcome. Examined genetic polymorphisms did not predict development of splenomegaly.

Citations

Citations to this article as recorded by  
  • Association of VEGF promoter polymorphisms with gastrointestinal tract cancer risk and therapy response: a systematic review
    Deepanshi Mahajan, Vasudha Sambyal, Kamlesh Guleria
    Egyptian Journal of Medical Human Genetics.2025;[Epub]     CrossRef
  • Association of Vascular Endothelial Growth Factor Gene Polymorphisms with Esophageal Squamous Cell Cancer Risk in North-West Indians: A Case–Control Study
    Deepanshi Mahajan, Vasudha Sambyal, Meena Sudan, Manjit Singh Uppal, Kamlesh Guleria
    DNA and Cell Biology Reports.2025; 6(1): 22.     CrossRef
  • Oxaliplatin‑induced changes in splenic volume and liver fibrosis indices: retrospective analyses of colon cancer patients receiving adjuvant chemotherapy
    Kadriye Bir Yücel, Atiye Cenay Karabörk Kilic, Osman Sütcüoglu, Ozan Yazıcı, Koray Kilic, Gözde Savaş, Aytug Uner, Nazan Günel, Ahmet Özet, Nuriye Özdemir
    Journal of Chemotherapy.2024; 36(3): 249.     CrossRef
  • Effects of methanolic leaf extract and fractions of Irvingia gabonensis on hematological parameters in Wistar rats with splenomegaly
    Fidelia Okoben, InnocentMary Ejiofor, Ikechukwu Mbagwu, Daniel Ajaghaku, Fredrick Anowi
    Sciences of Pharmacy.2024; 3(1): 11.     CrossRef
  • Clinical and genetic factors involved in Porto-sinusoidal vascular disorder after oxaliplatin exposure
    A. Puente, J.I. Fortea, C. Del Pozo, M. Serrano, M. Alonso-Peña, A. Giráldez, L. Tellez, J. Martinez, M. Magaz, L. Ibañez, J. Garcia, E. Llop, C. Alvarez-Navascues, M. Romero, E. Rodriguez, M.T. Arias Loste, A. Antón, V. Echavarria, C. López, A. Albillos,
    Digestive and Liver Disease.2024; 56(10): 1721.     CrossRef
  • The “appearing” and “disappearing” ascites in the treatment of colorectal cancer: a case report
    Hong-Ming Cui, Xin-Peng Shu, Zheng-Qiang Wei, Xing-Ye Wu
    Frontiers in Oncology.2024;[Epub]     CrossRef
  • A contrast-enhanced CT-based whole-spleen radiomics signature for early prediction of oxaliplatin-related thrombocytopenia in patients with gastrointestinal malignancies: a retrospective study
    Yuhong Dai, Yiqi Cheng, Ziling Zhou, Zhen Li, Yan Luo, Hong Qiu
    PeerJ.2023; 11: e16230.     CrossRef
  • Natural Language Processing of Large-Scale Structured Radiology Reports to Identify Oncologic Patients With or Without Splenomegaly Over a 10-Year Period
    Simon Sun, Kaelan Lupton, Karen Batch, Huy Nguyen, Lior Gazit, Natalie Gangai, Jessica Cho, Kevin Nicholas, Farhana Zulkernine, Varadan Sevilimedu, Amber Simpson, Richard K. G. Do
    JCO Clinical Cancer Informatics.2022;[Epub]     CrossRef
  • Model establishment and microarray analysis of mice with oxaliplatin‑induced hepatic sinusoidal obstruction syndrome
    Chen Zhu, Xinwei Cheng, Ping Gao, Qianyan Gao, Ximin Wang, Dong Liu, Xiuhua Ren, Chengliang Zhang
    Molecular Medicine Reports.2022;[Epub]     CrossRef
  • Oxaliplatin-induced hepatic sinusoidal obstruction syndrome
    Chen Zhu, Xiuhua Ren, Dong Liu, Chengliang Zhang
    Toxicology.2021; 460: 152882.     CrossRef
  • Association between single nucleotide polymorphisms (SNPs) of IL1, IL12, IL28 and TLR4 and symptoms of congenital cytomegalovirus infection
    Dominika Jedlińska-Pijanowska, Beata Kasztelewicz, Justyna Czech-Kowalska, Maciej Jaworski, Klaudia Charusta-Sienkiewicz, Anna Dobrzańska, Michael Nevels
    PLOS ONE.2020; 15(5): e0233096.     CrossRef
  • Oxaliplatin-induced increase in splenic volume: experiences from multicenter study in Japan
    Ryo Ohta, Takeshi Yamada, Keisuke Hara, Takuma Iwai, Kohji Tanakaya, Keiichiro Ishibashi, Kazuhiko Yoshimatsu, Chihiro Kosugi, Masahiro Tsubaki, Hideo Nakajima, Masatoshi Oya, Hiroshi Yoshida, Keiji Koda, Hideyuki Ishida
    International Journal of Clinical Oncology.2020; 25(12): 2075.     CrossRef
  • Oxaliplatin-induced haematological toxicity and splenomegaly in mice
    Justin G. Lees, Daniel White, Brooke A. Keating, Mallory E. Barkl-Luke, Preet G. S. Makker, David Goldstein, Gila Moalem-Taylor, Senthilnathan Palaniyandi
    PLOS ONE.2020; 15(9): e0238164.     CrossRef
  • Olive Oil‐Based Ultrafine Theranostic Photo Nanoemulsions: A Versatile Tumor Maneuvering Nanoplatform for Precise Controlled Drug Release in Tumor and Complete Tumor Eradication Mediated by Photo‐Chemotherapy
    N. Sanoj Rejinold, Kondareddy Cherukula, Jong Hoon Ha, In‐Kyu Park, Yeu‐Chun Kim
    Advanced Therapeutics.2019;[Epub]     CrossRef
  • Protective effect of Korean red ginseng on oxaliplatin-mediated splenomegaly in colon cancer
    Jeonghyun Kang, Joon Seong Park, Sung Gwe Ahn, Jin Hong Lim, Seung Hyuk Baik, Dong Sup Yoon, Kang Young Lee, Joon Jeong
    Annals of Surgical Treatment and Research.2018; 95(3): 161.     CrossRef
  • Automatized spleen segmentation in non-contrast-enhanced MR volume data using subject-specific shape priors
    Oliver Gloger, Klaus Tönnies, Robin Bülow, Henry Völzke
    Physics in Medicine & Biology.2017; 62(14): 5861.     CrossRef
  • UGT1A1 gene polymorphism is associated with toxicity and clinical efficacy of irinotecan-based chemotherapy in patients with advanced colorectal cancer
    Chunlei Xu, Xushan Tang, Yanli Qu, Saifuding Keyoumu, Ning Zhou, Yong Tang
    Cancer Chemotherapy and Pharmacology.2016; 78(1): 119.     CrossRef
  • 13,428 View
  • 160 Download
  • 19 Web of Science
  • 17 Crossref
Close layer
Concurrent Chemoradiotherapy Versus Chemotherapy Alone for Unresectable Locally Advanced Pancreatic Cancer: A Retrospective Cohort Study
Younak Choi, Do-Youn Oh, Kyubo Kim, Eui Kyu Chie, Tae-Yong Kim, Kyung-Hun Lee, Sae-Won Han, Seock-Ah Im, Tae-You Kim, Sung Whan Ha, Yung-Jue Bang
Cancer Res Treat. 2016;48(3):1045-1055.   Published online October 16, 2015
DOI: https://doi.org/10.4143/crt.2015.226
AbstractAbstract PDFPubReaderePub
Purpose
The optimal treatment strategy for locally advanced pancreatic cancer (LAPC), particularly the role of concurrent chemoradiotherapy (CCRT), remains debatable. We compared the clinical outcomes of CCRT and palliative chemotherapy alone (CA) in patients with unresectable LAPC. Materials and Methods Patients with LAPC who were consecutively treated between 2003 and 2010 were included. Resectability was evaluated according to National Comprehensive Cancer Network ver. 1.2012. The clinical outcomes for each treatment group (CCRT vs. CA) were evaluated retrospectively.
Results
Sixty-three patients (58.9%) and 44 patients (41.1%) were treated with CCRT and CA, respectively. The CCRT cohort included patients who were treated with CCRT with or without chemotherapy backbone (CCRT alone, induction chemotherapy-CCRT, CCRT-maintenance chemotherapy, and induction-CCRT-maintenance chemotherapy). Median progression-free survival (PFS) and overall survival (OS) of all patients were 7.2 months and 13.1 months. PFS of the CCRT and CA groups was 9.0 months and 4.4 months, respectively (p=0.020). OS of the CCRT and CA groups was 15.4 months and 9.3 months, respectively (p=0.011). In multivariate analysis, the adjusted hazard ratio of CCRT was 0.536 (p=0.003) for OS and 0.667 (p=0.078) for PFS. Although the pattern of failure was similar in the CCRT and CA groups, the times to both local and distant failure were significantly longer in the CCRT group. Conclusion In patients with unresectable LAPC, those who underwent CCRT during their entire treatment courses had longer OS than patients treated with chemotherapy alone.

Citations

Citations to this article as recorded by  
  • Dose-Escalated SBRT for Borderline and Locally Advanced Pancreatic Cancer: Resectability Rate and Pathological Results of a Multicenter Prospective Study
    Barbara Salas-Salas, Laura Ferrera-Alayon, Alberto Espinosa-Lopez, Maria Luisa Perez-Rodriguez, Antonio Alayón Afonso, Andres Vera-Rosas, Gabriel Garcia-Plaza, Rodolfo Chicas-Sett, Maria Soledad Martinez-Martin, Elisa Salcedo, Andrea Kannemann, Marta Llor
    Cancers.2025; 17(2): 191.     CrossRef
  • Dose-escalated SBRT for borderline and locally advanced pancreatic cancer. Feasibility, safety and preliminary clinical results of a multicenter study
    B. Salas, L. Ferrera-Alayón, A. Espinosa-López, A. Vera-Rosas, E. Salcedo, A. Kannemann, A. Alayon, R. Chicas-Sett, M. LLoret, P.C. Lara
    Clinical and Translational Radiation Oncology.2024; 45: 100753.     CrossRef
  • Survival benefits of radiotherapy in locally advanced unresectable and metastatic pancreatic cancer: a single-institution cohort and SEER database analysis
    Bi-Yang Cao, Le-Tian Zhang, Chen-Chen Wu, Jing Wang, Lin Yang
    Frontiers in Oncology.2024;[Epub]     CrossRef
  • Comparing concurrent chemoradiotherapy, 125I seed implantation combined with chemotherapy, and chemotherapy alone efficacy in treating unresectable locally advanced pancreatic cancer
    Yanfen Zheng, Rui Huang, Wenxue Zou, Chao Liu, Hongxin Niu, Jinbo Yue
    Precision Radiation Oncology.2022; 6(2): 144.     CrossRef
  • Concurrent Nab-paclitaxel and Radiotherapy
    William T. Arscott, Kevin T. Nead, Adham Bear, Sriram Venigalla, Jacob Shabason, John N. Lukens, John P. Plastaras, Andrzej Wojcieszynski, James Metz, Mark O’Hara, Kim A. Reiss, Ursina Teitelbaum, Arturo Loaiza-Bonilla, Jeffrey Drebin, Major K. Lee, Stuti
    American Journal of Clinical Oncology.2021; 44(9): 469.     CrossRef
  • Therapeutic Co-targeting of WEE1 and ATM Downregulates PD-L1 Expression in Pancreatic Cancer
    Mei Hua Jin, Ah-Rong Nam, Ji Eun Park, Ju-Hee Bang, Yung-Jue Bang, Do-Youn Oh
    Cancer Research and Treatment.2020; 52(1): 149.     CrossRef
  • Current trends and issues of conversion surgery for patients with locally advanced unresectable pancreatic cancer
    Toshimichi ASANO, Satoshi HIRANO, Toru NAKAMURA, Takehiro NOJI, Keisuke OKAMURA, Takahiro TSUCHIKAWA, Yuma EBIHARA, Toshiaki SHICHINOHE
    Suizo.2018; 33(1): 48.     CrossRef
  • Survival benefit of conversion surgery for patients with initially unresectable pancreatic cancer who responded favorably to nonsurgical treatment
    Toshimichi Asano, Satoshi Hirano, Toru Nakamura, Keisuke Okamura, Takahiro Tsuchikawa, Takehiro Noji, Yoshitsugu Nakanishi, Kimitaka Tanaka, Toshiaki Shichinohe
    Journal of Hepato-Biliary-Pancreatic Sciences.2018; 25(7): 342.     CrossRef
  • Which patients with locally advanced pancreatic cancer treated with induction chemotherapy are most likely to benefit from post-induction chemoradiotherapy?
    Sophie Otter, Irene Chong, Ria Kalaitzaki, Diana Tait
    International Journal of Hepatobiliary and Pancreatic Diseases.2018; 8(1): 1.     CrossRef
  • Change in carbohydrate antigen 19-9 level as a prognostic marker of overall survival in locally advanced pancreatic cancer treated with concurrent chemoradiotherapy
    Yi-Jun Kim, Hyeon Kang Koh, Eui Kyu Chie, Do-Youn Oh, Yung-Jue Bang, Eun Mi Nam, Kyubo Kim
    International Journal of Clinical Oncology.2017; 22(6): 1069.     CrossRef
  • Risk factors of liver metastasis from advanced pancreatic adenocarcinoma: a large multicenter cohort study
    Dong S., Wang L., Guo Y. B., Ying H. F., Shen X. H., Meng Z. Q., Chen Hao, Chen Q. W., Li Z. S.
    World Journal of Surgical Oncology.2017;[Epub]     CrossRef
  • Risk factors for latent distant organ metastasis detected by staging laparoscopy in patients with radiologically defined locally advanced pancreatic ductal adenocarcinoma
    Ilhan Karabicak, Sohei Satoi, Hiroaki Yanagimoto, Tomohisa Yamamoto, Satoshi Hirooka, So Yamaki, Hisashi Kosaka, Kentaro Inoue, Yoichi Matsui, Masanori Kon
    Journal of Hepato-Biliary-Pancreatic Sciences.2016; 23(12): 750.     CrossRef
  • 12,441 View
  • 137 Download
  • 11 Web of Science
  • 12 Crossref
Close layer
Aberrant Epigenetic Modifications of LPHN2 Function as a Potential Cisplatin-Specific Biomarker for Human Gastrointestinal Cancer
Mi-Seong Jeon, Sang-Hyun Song, Jiyeon Yun, Jee-Youn Kang, Hwang-Phill Kim, Sae-Won Han, Tae-You Kim
Cancer Res Treat. 2016;48(2):676-686.   Published online September 22, 2015
DOI: https://doi.org/10.4143/crt.2015.153
AbstractAbstract PDFPubReaderePub
Purpose
Epigenetic alterations of specific genes have recently been identified as diagnostic biomarkers for human cancers. However, there are currently no standardized epigenetic biomarkers for drug sensitivity in human gastrointestinal cancer. Therefore, the aim of this study is to identify a novel epigenetic biomarker in gastrointestinal cancer.
Materials and Methods
Using bisulfite sequencing and pyrosequencing analysis, DNA methylation patterns of gastric, colon primary tissues and their cancer cells were analyzed, and histone modifications were analyzed using chromatin immunoprecipitation assay. In addition, cancer cells were exposed to cisplatin and treated with a DNA methyltransferase inhibitor.
Results
We report that in human gastric and colon cancers, latrophilin 2 (LPHN2) is silenced by epigenetic modifications, including CpG island methylation and aberrant histone modifications. We also confirmed that LPHN2 was silenced by DNA hypermethylation in primary gastric and colon tumor tissues compared to their normal counterparts. Interestingly, we found that cancer cells with methylated LPHN2 showed higher sensitivity to cisplatin. Also, 5-aza- 2′-deoxycytidine combined with cisplatin decreased the cytotoxicity of cisplatin in cancer cells with methylated LPHN2. In addition, LPHN2 knockdown in cancer cells with high LPHN2 expression sensitized these cells to the anti-proliferative effects of cisplatin.
Conclusion
In human gastrointestinal cancer, we found that LPHN2 is regulated by epigenetic modifications, and that cancer cells with lower LPHN2 expression show higher sensitivity to cisplatin. Therefore, the methylation status of LPHN2 is a potential novel epigenetic biomarker for cisplatin treatment in human gastric and colon cancers.

Citations

Citations to this article as recorded by  
  • Latrophilin‐3 as a downstream effector of the androgen receptor induces urothelial tumorigenesis
    Takuro Goto, Masato Yasui, Yuki Teramoto, Yujiro Nagata, Taichi Mizushima, Hiroshi Miyamoto
    Molecular Carcinogenesis.2024; 63(10): 1847.     CrossRef
  • Latrophilins as Downstream Effectors of Androgen Receptors including a Splice Variant, AR-V7, Induce Prostate Cancer Progression
    Yuki Teramoto, Mohammad Amin Elahi Najafi, Takuo Matsukawa, Adhya Sharma, Takuro Goto, Hiroshi Miyamoto
    International Journal of Molecular Sciences.2024; 25(13): 7289.     CrossRef
  • Latrophilin-3 as a downstream effector of the androgen receptor induces bladder cancer progression
    Takuro Goto, Yuki Teramoto, Yujiro Nagata, Hiroshi Miyamoto
    Discover Oncology.2024;[Epub]     CrossRef
  • Histone modification: Biomarkers and potential therapies in colorectal cancer
    Xin An, Xiaohua Lan, Zizhen Feng, Xiaohong Li, Qisheng Su
    Annals of Human Genetics.2023; 87(6): 274.     CrossRef
  • Recent advances of nucleic acid-based cancer biomarkers and biosensors
    Jingkun Zhao, Kai Xia, Peng He, Gang Wei, Xin Zhou, Xiaodong Zhang
    Coordination Chemistry Reviews.2023; 497: 215456.     CrossRef
  • Genetic Analysis Reveals Rare Variants in T-Cell Response Gene MR1 Associated with Poor Overall Survival after Urothelial Cancer Diagnosis
    Lisa Bang, Manu Shivakumar, Tullika Garg, Dokyoon Kim
    Cancers.2021; 13(8): 1864.     CrossRef
  • Chromatin accessibility changes are associated with enhanced growth and liver metastasis capacity of acid-adapted colorectal cancer cells
    Zhi-Hang Zhou, Qing-Liang Wang, Lin-Hong Mao, Xiao-Qin Li, Peng Liu, Jin-Wen Song, Xue Liu, Feng Xu, Jing Lei, Song He
    Cell Cycle.2019; 18(4): 511.     CrossRef
  • Copy Number Variation Pattern for Discriminating MACROD2 States of Colorectal Cancer Subtypes
    ShiQi Zhang, XiaoYong Pan, Tao Zeng, Wei Guo, Zijun Gan, Yu-Hang Zhang, Lei Chen, YunHua Zhang, Tao Huang, Yu-Dong Cai
    Frontiers in Bioengineering and Biotechnology.2019;[Epub]     CrossRef
  • Pharmacoepigenetics and pharmacoepigenomics of gastrointestinal cancers
    Angela Lopomo, Fabio Coppedè
    Expert Review of Gastroenterology & Hepatology.2018; 12(1): 49.     CrossRef
  • Elevation of Peripheral BDNF Promoter Methylation Predicts Conversion from Amnestic Mild Cognitive Impairment to Alzheimer’s Disease: A 5-Year Longitudinal Study
    Bing Xie, Yao Xu, Zanchao Liu, Wenxuan Liu, Lei Jiang, Rui Zhang, Dongsheng Cui, Qingfu Zhang, Shunjiang Xu, Ling-Qiang Zhu
    Journal of Alzheimer’s Disease.2017; 56(1): 391.     CrossRef
  • Identification and evolution of latrophilin receptor gene involved in Tribolium castaneum devolopment and female fecundity
    Shanshan Gao, Xing Liu, Juanjuan Liu, Wenfeng Xiong, Xiaowen Song, Wei Wu, Luting Wei, Bin Li
    genesis.2017;[Epub]     CrossRef
  • Pharmacogenetics of response to neoadjuvant paclitaxel treatment for locally advanced breast cancer
    Andric C. Perez-Ortiz, Israel Ramírez, Juan C. Cruz-López, Cynthia Villarreal-Garza, Alexandra Luna-Angulo, Esmeralda Lira-Romero, Salvador Jiménez-Chaidez, José Díaz-Chávez, Juan A. Matus-Santos, Laura Sánchez-Chapul, Patricia Mendoza-Lorenzo, Francisco
    Oncotarget.2017; 8(63): 106454.     CrossRef
  • CircRNA_100269 is downregulated in gastric cancer and suppresses tumor cell growth by targeting miR-630
    Yan Zhang, Hao Liu, Wende Li, Jiang Yu, Jin Li, Zhiyong Shen, Gentai Ye, Xiaolong Qi, Guoxin Li
    Aging.2017; 9(6): 1585.     CrossRef
  • 13,197 View
  • 145 Download
  • 17 Web of Science
  • 13 Crossref
Close layer
The Impact of Diabetes Mellitus and Metformin Treatment on Survival of Patients with Advanced Pancreatic Cancer Undergoing Chemotherapy
Younak Choi, Tae-Yong Kim, Do-Youn Oh, Kyung-Hun Lee, Sae-Won Han, Seock-Ah Im, Tae-You Kim, Yung-Jue Bang
Cancer Res Treat. 2016;48(1):171-179.   Published online March 13, 2015
DOI: https://doi.org/10.4143/crt.2014.292
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
A causal relationship between diabetes mellitus (DM) and pancreatic cancer is well established. However, in patients with advanced pancreatic cancer (APC) who receive palliative chemotherapy, the impact of DM on the prognosis of APC is unclear. Materials and Methods We retrospectively enrolled APC patients who received palliative chemotherapy between 2003 and 2010. The patients were stratified according to the status of DM, in accordance with 2010 DM criteria (American Heart Association/American Diabetes Association). DM at least 2 years’ duration prior to diagnosis of APC was defined as remote-onset DM (vs. recent-onset).
Results
Of the 349 APC patients, 183 (52.4%) had DM. Among the patients with DM, 160 patients had DM at the time of diagnosis of APC (remote-onset, 87; recent-onset, 73) and the remaining 23 patients developed DM during treatment of APC. Ultimately, 73.2% of patients (134/183) with DM received antidiabetic medication, including metformin (56 patients, 41.8%), sulfonylurea (62, 45.5%), and insulin (43, 32.1%). In multivariate analysis, cancer extent (hazard ratio [HR], 1.792; 95% confidence interval [CI], 1.313 to 2.445; p < 0.001) showed association with decreased overall survival (OS), whereas a diagnosis of DM (HR, 0.788; 95% CI, 0.615 to 1.009; p=0.059) conferred positive tendency on the OS. Metformin treatment itself conferred better OS in comparison within DM patients (HR 0.693; 95% CI, 0.492 to 0.977; p=0.036) and even in all APC patients (adjusted HR, 0.697; 95% CI, 0.491 to 1.990; p=0.044). Conclusion For APC patients receiving palliative chemotherapy, metformin treatment is associated with longer OS. Patients with DM tend to survive longer than those without DM.

Citations

Citations to this article as recorded by  
  • Metformin use and pancreatic ductal adenocarcinoma outcomes: a narrative review
    Dooyeon Lee, Mun Sem Liew, Spiros Fourlanos, Julian Choi
    ANZ Journal of Surgery.2025; 95(3): 313.     CrossRef
  • Hyperglycemia predicts adverse prognosis in advanced pancreatic cancer patients
    Xinzhe Zhu, Huaxiang Xu, Zhiwen Xiao, He Liu, Quanxing Ni, Xianjun Yu, Guopei Luo
    Endocrine.2023; 79(2): 296.     CrossRef
  • Influence of diabetes mellitus and effectiveness of metformin on hepatocellular carcinoma
    Masafumi Ono, Koji Fujita, Kiyoyuki Kobayashi, Tsutomu Masaki
    Hepatology Research.2023; 53(7): 579.     CrossRef
  • Diabetes duration and weight loss are associated with onset age and remote metastasis of pancreatic cancer in patients with diabetes mellitus
    Minglei Ma, Wei Li, Lingling Xu, Fan Ping, Huabing Zhang, Yuxiu Li
    Journal of Diabetes.2022; 14(4): 261.     CrossRef
  • Diabetes Mellitus and Pancreatic Ductal Adenocarcinoma—Prevalence, Clinicopathological Variables, and Clinical Outcomes
    Anna Badowska-Kozakiewicz, Marta Fudalej, Daria Kwaśniewska, Marek Durlik, Anna Nasierowska-Guttmejer, Agata Mormul, Emilia Włoszek, Aleksandra Czerw, Tomasz Banaś, Andrzej Deptała
    Cancers.2022; 14(12): 2840.     CrossRef
  • Prognostic value of metformin in cancers: An updated meta-analysis based on 80 cohort studies
    Jing Yang, Hang Yang, Ling Cao, Yuzhen Yin, Ying Shen, Wei Zhu
    Medicine.2022; 101(49): e31799.     CrossRef
  • Impact of Diabetes and Insulin Use on Prognosis in Patients With Resected Pancreatic Cancer: An Ancillary Analysis of NRG Oncology RTOG 9704
    Danielle S. Bitterman, Kathryn A. Winter, Theodore S. Hong, Charles S. Fuchs, William F. Regine, Ross A. Abrams, Howard Safran, John P. Hoffman, Al B. Benson, Timothy Kasunic, Mary Mulcahy, James F. Strauss, Thomas DiPetrillo, Philip J. Stella, Yuhchyau C
    International Journal of Radiation Oncology*Biology*Physics.2021; 109(1): 201.     CrossRef
  • Effect of type 2 diabetes mellitus on survival in metastatic pancreatic cancer
    Ayşegül SAKİN, Suleyman SAHİN, Abdullah SAKİN, Muhammed ATCİ, Çağlayan GEREDELİ, Şener CİHAN
    Journal of Surgery and Medicine.2021; 5(1): 17.     CrossRef
  • Pancreatic Tumorigenesis: Oncogenic KRAS and the Vulnerability of the Pancreas to Obesity
    Yongde Luo, Xiaokun Li, Jianjia Ma, James L. Abbruzzese, Weiqin Lu
    Cancers.2021; 13(4): 778.     CrossRef
  • Repurposing metformin for the treatment of gastrointestinal cancer
    Ademar Dantas Cunha Júnior, Arinilda Campos Bragagnoli, Felipe Osório Costa, José Barreto Campello Carvalheira
    World Journal of Gastroenterology.2021; 27(17): 1883.     CrossRef
  • Metformin Use and the Outcome of Metastatic Renal Cell Carcinoma Treated with Sunitinib or Pazopanib
    Ondřej Fiala, Pavel Ostašov, Aneta Rozsypalová, Milan Hora, Ondrej Sorejs, Jan Šustr, Barbora Bendová, Ivan Trávníček, Jan Filipovský, Jindřich Fínek, Tomáš Büchler
    Cancer Management and Research.2021; Volume 13: 4077.     CrossRef
  • Magic of a Common Sugar Pill in Cancer: Can Metformin Raise Survival in Pancreatic Cancer Patients?
    Mallika Gyawali, Nanditha Venkatesan, Opemipo D Ogeyingbo, Renu Bhandari, Rinky A Botleroo, Roaa Kareem, Rowan Ahmed, Abeer O Elshaikh
    Cureus.2021;[Epub]     CrossRef
  • Identification of Key Genes Involved in Diabetic Peripheral Neuropathy Progression and Associated with Pancreatic Cancer


    Liumeng Jian, Guangda Yang
    Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy.2020; Volume 13: 463.     CrossRef
  • Oncological benefit of metformin in patients with pancreatic ductal adenocarcinoma and comorbid diabetes mellitus
    Fumihiro Terasaki, Teiichi Sugiura, Yukiyasu Okamura, Takaaki Ito, Yusuke Yamamoto, Ryo Ashida, Katsuhisa Ohgi, Katsuhiko Uesaka
    Langenbeck's Archives of Surgery.2020; 405(3): 313.     CrossRef
  • The Impact of obesity and diabetes mellitus on pancreatic cancer: Molecular mechanisms and clinical perspectives
    Bao Quoc Lam, Sushant K. Shrivastava, Anju Shrivastava, Sharmila Shankar, Rakesh K. Srivastava
    Journal of Cellular and Molecular Medicine.2020; 24(14): 7706.     CrossRef
  • Association between Metformin Use and Clinical Outcomes Following Pancreaticoduodenectomy in Patients with Type 2 Diabetes and Pancreatic Ductal Adenocarcinoma
    Daegwang Yoo, Nayoung Kim, Dae Wook Hwang, Ki Byung Song, Jae Hoon Lee, Woohyung Lee, Jaewoo Kwon, Yejong Park, Sarang Hong, Jong Woo Lee, Kyungyeon Hwang, Dakyum Shin, Eunyoung Tak, Song Cheol Kim
    Journal of Clinical Medicine.2020; 9(6): 1953.     CrossRef
  • The Role of Dysfunctional Adipose Tissue in Pancreatic Cancer: A Molecular Perspective
    Davide Brocco, Rosalba Florio, Laura De Lellis, Serena Veschi, Antonino Grassadonia, Nicola Tinari, Alessandro Cama
    Cancers.2020; 12(7): 1849.     CrossRef
  • Cohort Study of Antihyperglycemic Medication and Pancreatic Cancer Patients Survival
    Audrius Dulskas, Ausvydas Patasius, Donata Linkeviciute-Ulinskiene, Lina Zabuliene, Giedre Smailyte
    International Journal of Environmental Research and Public Health.2020; 17(17): 6016.     CrossRef
  • Relationships are between metformin use and survival in pancreatic cancer patients concurrent with diabetes
    Yu-Qi Shi, Xiao-Chong Zhou, Peng Du, Min-Yue Yin, Lan Xu, Wen-Jie Chen, Chun-Fang Xu
    Medicine.2020; 99(37): e21687.     CrossRef
  • Metformin Use and Pancreatic Cancer Survival among Non-Hispanic White and African American U.S. Veterans with Diabetes Mellitus
    Adetunji T. Toriola, Suhong Luo, Theodore S. Thomas, Bettina F. Drake, Su-Hsin Chang, Kristen M. Sanfilippo, Kenneth R. Carson
    Cancer Epidemiology, Biomarkers & Prevention.2020; 29(1): 169.     CrossRef
  • Metformin and pancreatic cancer survival: Real effect or immortal time bias?
    Min Wei, Yu Liu, Yongyi Bi, Zhi‐Jiang Zhang
    International Journal of Cancer.2019; 145(7): 1822.     CrossRef
  • The effect of diabetes mellitus on pharmacokinetics, pharmacodynamics and adverse drug reactions of anticancer drugs
    Habibeh Mashayekhi‐Sardoo, Amir Hooshang Mohammadpour, Homa Nomani, Amirhossein Sahebkar
    Journal of Cellular Physiology.2019; 234(11): 19339.     CrossRef
  • The impact of diabetes mellitus on clinical outcomes following chemotherapy for the patients with pancreatic cancer: a meta-analysis
    Jichun Ma, Jing Wang, Long Ge, Bo Long, Junqiang Zhang
    Acta Diabetologica.2019; 56(10): 1103.     CrossRef
  • Obesity and Pancreatic Cancer
    Mu Xu, Xiaoman Jung, O. Joe Hines, Guido Eibl, Yijun Chen
    Pancreas.2018; 47(2): 158.     CrossRef
  • Impact of Concurrent Medication Use on Pancreatic Cancer Survival—SEER-Medicare Analysis
    Muhammad S. Beg, Arjun Gupta, David Sher, Sadia Ali, Saad Khan, Ang Gao, Tyler Stewart, Chul Ahn, Jarett Berry, Eric M. Mortensen
    American Journal of Clinical Oncology.2018; 41(8): 766.     CrossRef
  • Metformin as an Adjunctive Therapy for Pancreatic Cancer: A Review of the Literature on Its Potential Therapeutic Use
    Philip J. Broadhurst, Andrew R. Hart
    Digestive Diseases and Sciences.2018; 63(11): 2840.     CrossRef
  • Exploring the bi-directional relationship between pancreatic cancer and diabetes mellitus: a retrospective study
    Kellam Harry, Yim Kein-Leong
    Journal of Diabetes & Metabolic Disorders.2018; 17(2): 247.     CrossRef
  • No association between metformin use and survival in patients with pancreatic cancer
    Martine A. Frouws, Babs G. Sibinga Mulder, Esther Bastiaannet, Marjolein M.J. Zanders, Myrthe P.P. van Herk-Sukel, Eleonora M. de Leede, Bert A. Bonsing, J. Sven. D. Mieog, Cornelis J.H. Van de Velde, Gerrit-Jan Liefers
    Medicine.2017; 96(10): e6229.     CrossRef
  • Chloride intracellular channel 1 regulates the antineoplastic effects of metformin in gallbladder cancer cells
    Yongchen Liu, Zheng Wang, Maolan Li, Yuanyuan Ye, Yi Xu, Yichi Zhang, Ruiyan Yuan, Yunpeng Jin, Yajuan Hao, Lin Jiang, Yunping Hu, Shili Chen, Fatao Liu, Yijian Zhang, Wenguang Wu, Yingbin Liu
    Cancer Science.2017; 108(6): 1240.     CrossRef
  • The effect of metformin on survival of patients with pancreatic cancer: a meta-analysis
    Xiaogang Li, Tong Li, Zhiqiang Liu, Shanmiao Gou, Chunyou Wang
    Scientific Reports.2017;[Epub]     CrossRef
  • The Effect of Metformin on Mortality Among Diabetic Cancer Patients: A Systematic Review and Meta-analysis
    Xun Cao, Yaopan Wu, Jing Wang, Kuiyuan Liu, Xin Wang
    JNCI Cancer Spectrum.2017;[Epub]     CrossRef
  • Association of elevated risk of pancreatic cancer in diabetic patients: A systematic review and meta-analysis
    Jiaxin Tan, Yu You, Fei Guo, Jianhua Xu, Haisu Dai, Ping Bie
    Oncology Letters.2017; 13(3): 1247.     CrossRef
  • Pancreatic Carcinoma and Diabetes Mellitus
    Laszlo Czako
    Gastroenterology & Hepatology: Open Access.2017;[Epub]     CrossRef
  • Association between metformin use and mortality in patients with type 2 diabetes mellitus and localized resectable pancreatic cancer: a nationwide population-based study in korea
    Won Il Jang, Mi-Sook Kim, Shin Hee Kang, Ae Jung Jo, Yun Jung Kim, Ha Jin Tchoe, Chan Mi Park, Hyo Jeong Kim, Jin A Choi, Hyung Jin Choi, Eun-Kyung Paik, Young Seok Seo, Hyung Jun Yoo, Jin-Kyu Kang, Chul Ju Han, Yeon Ju Kim, Sang Beom Kim, Min Jung Ko
    Oncotarget.2017; 8(6): 9587.     CrossRef
  • Metformin is associated with survival benefit in pancreatic cancer patients with diabetes: a systematic review and meta-analysis
    Ping-Ting Zhou, Bo Li, Fu-Rao Liu, Mei-Chao Zhang, Qian Wang, Yan-Yan Li, Ci Xu, Yuan-Hua Liu, Yuan Yao, Dong Li
    Oncotarget.2017; 8(15): 25242.     CrossRef
  • Effects of metformin on survival outcomes of pancreatic cancer: a meta-analysis
    Yi-Wei Dong, Yan-Qiang Shi, Li-Wen He, Xi-Yu Cui, Pei-Zhu Su
    Oncotarget.2017; 8(33): 55478.     CrossRef
  • Prognostic significance of anti-diabetic medications in pancreatic cancer: A meta-analysis
    Dong-Chu Zhou, Hui Gong, Chong-Qing Tan, Jian-Quan Luo
    Oncotarget.2017; 8(37): 62349.     CrossRef
  • Effects of metformin on survival outcomes of pancreatic cancer patients with diabetes: A meta-analysis
    Wenxiu Xin, Luo Fang, Qilu Fang, Xiaowei Zheng, Ping Huang
    Molecular and Clinical Oncology.2017;[Epub]     CrossRef
  • Obesity and Cancer: An Angiogenic and Inflammatory Link
    Dai Fukumura, Joao Incio, Ram C. Shankaraiah, Rakesh K. Jain
    Microcirculation.2016; 23(3): 191.     CrossRef
  • Metformin in pancreatic cancer treatment: from clinical trials through basic research to biomarker quantification
    Archana Bhaw-Luximon, Dhanjay Jhurry
    Journal of Cancer Research and Clinical Oncology.2016; 142(10): 2159.     CrossRef
  • Metformin Use Is Associated with Improved Survival in Patients Undergoing Resection for Pancreatic Cancer
    Marcelo Cerullo, Faiz Gani, Sophia Y. Chen, Joe Canner, Timothy M. Pawlik
    Journal of Gastrointestinal Surgery.2016; 20(9): 1572.     CrossRef
  • Effect of Diabetes on Survival after Resection of Pancreatic Adenocarcinoma. A Prospective, Observational Study
    Gianpaolo Balzano, Erica Dugnani, Alessandra Gandolfi, Marina Scavini, Valentina Pasquale, Francesca Aleotti, Daniela Liberati, Gaetano Di Terlizzi, Giovanna Petrella, Michele Reni, Claudio Doglioni, Emanuele Bosi, Massimo Falconi, Lorenzo Piemonti, Surin
    PLOS ONE.2016; 11(11): e0166008.     CrossRef
  • Type 2 diabetes mellitus is associated with increased risk of pancreatic cancer: A veteran administration registry study
    Issam Makhoul, Abdulraheem Yacoub, Eric Siegel
    SAGE Open Medicine.2016;[Epub]     CrossRef
  • Inhibitory effect of metformin combined with gemcitabine on pancreatic cancer cells in vitro and in vivo
    Yuqi Shi, Zhilong He, Zhenyu Jia, Chunfang Xu
    Molecular Medicine Reports.2016; 14(4): 2921.     CrossRef
  • Diabetes mellitus and metformin in hepatocellular carcinoma
    Koji Fujita, Hisakazu Iwama, Hisaaki Miyoshi, Joji Tani, Kyoko Oura, Tomoko Tadokoro, Teppei Sakamoto, Takako Nomura, Asahiro Morishita, Hirohito Yoneyama, Tsutomu Masaki
    World Journal of Gastroenterology.2016; 22(27): 6100.     CrossRef
  • High prevalence of diabetes mellitus and impaired glucose tolerance in liver cancer patients: A hospital based study of 4610 patients with benign tumors or specific cancers
    Chen Roujun, Yi Yanhua, Li Bixun
    F1000Research.2016; 5: 1397.     CrossRef
  • (Ir)relevance of Metformin Treatment in Patients with Metastatic Pancreatic Cancer: An Open-Label, Randomized Phase II Trial
    Michele Reni, Erica Dugnani, Stefano Cereda, Carmen Belli, Gianpaolo Balzano, Roberto Nicoletti, Daniela Liberati, Valentina Pasquale, Marina Scavini, Paola Maggiora, Valeria Sordi, Vito Lampasona, Domenica Ceraulo, Gaetano Di Terlizzi, Claudio Doglioni,
    Clinical Cancer Research.2016; 22(5): 1076.     CrossRef
  • Can metformin improve ‘the tomorrow’ of patients treated for oesophageal cancer?
    L. Van De Voorde, L. Janssen, R. Larue, R. Houben, J. Buijsen, M. Sosef, B. Vanneste, M.-C. Schraepen, M. Berbée, P. Lambin
    European Journal of Surgical Oncology (EJSO).2015; 41(10): 1333.     CrossRef
  • Can metformin change the prognosis of pancreatic cancer? Retrospective study for pancreatic cancer patients with pre-existing diabetes mellitus type 2
    Sang Hoon Lee, Sang Hyun Yoon, Hee Seung Lee, Moon Jae Chung, Jeong Youp Park, Seung Woo Park, Si Young Song, Jae Bock Chung, Seungmin Bang
    Digestive and Liver Disease.2015;[Epub]     CrossRef
  • Metformin Increases Sensitivity of Pancreatic Cancer Cells to Gemcitabine by Reducing CD133+ Cell Populations and Suppressing ERK/P70S6K Signaling
    Xinqun Chai, Hongpeng Chu, Xuan Yang, Yuanpu Meng, Pengfei Shi, Shanmiao Gou
    Scientific Reports.2015;[Epub]     CrossRef
  • Obesity and cancer, a case for insulin signaling
    Y Poloz, V Stambolic
    Cell Death & Disease.2015; 6(12): e2037.     CrossRef
  • 16,917 View
  • 138 Download
  • 48 Web of Science
  • 51 Crossref
Close layer
Phase I Study of OPB-31121, an Oral STAT3 Inhibitor, in Patients with Advanced Solid Tumors
Do-Youn Oh, Se-Hoon Lee, Sae-Won Han, Mi-Jung Kim, Tae-Min Kim, Tae-You Kim, Dae Seog Heo, Miyuki Yuasa, Yasuo Yanagihara, Yung-Jue Bang
Cancer Res Treat. 2015;47(4):607-615.   Published online February 26, 2015
DOI: https://doi.org/10.4143/crt.2014.249
AbstractAbstract PDFPubReaderePub
Purpose
OPB-31121 is an oral STAT3 inhibitor with a good preclinical antitumor activity. This phase I dose-escalation study of OPB-31121 was conducted to determine maximum-tolerated dose (MTD), safety, pharmacokinetics, and preliminary antitumor efficacy in patients with advanced solid tumors. Materials and Methods Patients received OPB-31121 once daily for 28 days of each cycle followed by 2 weeks rest. A standard 3+3 design was used for dose-escalation. Safety and response were evaluated by the National Cancer Institute–Common Terminology Criteria for Adverse Events (NCICTCAE) ver. 3.0 and Response Evaluation Criteria in Solid Tumor (RECIST) ver. 1.0, respectively.
Results
Twenty-five patients were treated with OPB-31121 at five dose levels: 100 mg (n=4), 200 mg (n=3), 400 mg (n=3), 600 mg (n=7), and 800 mg (n=8). Seven patients discontinued treatment during cycle 1 for various reasons other than study drug-related adverse events. Among 18 patients who were evaluable for dose-limiting toxicity (DLT), three DLTs were observed: one DLT (grade 3 vomiting) at 600 mg and two DLTs (grade 3 vomiting, grade 3 diarrhea) at 800 mg. The MTD was determined as 800 mg/day. Common adverse events were gastrointestinal adverse event including nausea (84%), vomiting (80%), and diarrhea (72%). Pharmacokinetics did not demonstrate dose-proportionality of OPB-31121. Eight patients had stable disease and 10 patients had disease progression. Two patients (1 colon cancer, 1 rectal cancer) showed tumor shrinkage. One gastric cancer patient continued treatment up to cycle 13 before disease progression. Conclusion This study demonstrates feasibility of STAT3 inhibition in patients with advanced solid tumor. OPB-31121, at the MTD of 800 mg/day, was safe and relatively well tolerated, and has a preliminary antitumor activity.

Citations

Citations to this article as recorded by  
  • Expression of STAT3, IL27p28 and IL12p35 is deregulated and linked to autoimmune markers in chronic spontaneous urticaria
    Sahar Rastgoo, Mojgan Mohammadi, Marcus Maurer, Mahdi Atabaki, Jalil Tavakkol-Afshari, Maryam Khoshkhui
    Clinical and Experimental Dermatology.2025; 50(2): 357.     CrossRef
  • Insights into IL-6/JAK/STAT3 signaling in the tumor microenvironment: Implications for cancer therapy
    Win Lwin Thuya, Yang Cao, Paul Chi-Lui Ho, Andrea Li-Ann Wong, Lingzhi Wang, Jianbiao Zhou, Christophe Nicot, Boon Cher Goh
    Cytokine & Growth Factor Reviews.2025;[Epub]     CrossRef
  • CTSL Promotes Autophagy in Laryngeal Cancer Through the IL6‐JAK‐STAT3 Signalling Pathway
    Xueying Wang, Junrong Wang, Lei Wang, Ming Song, Hongxue Meng, Erliang Guo, Susheng Miao
    Journal of Cellular and Molecular Medicine.2025;[Epub]     CrossRef
  • Hepatocellular carcinoma: signaling pathways and therapeutic advances
    Jiaojiao Zheng, Siying Wang, Lei Xia, Zhen Sun, Kui Ming Chan, René Bernards, Wenxin Qin, Jinhong Chen, Qiang Xia, Haojie Jin
    Signal Transduction and Targeted Therapy.2025;[Epub]     CrossRef
  • STAT3 Inhibition Prevents Adaptive Resistance and Augments NK Cell Cytotoxicity to KRASG12C Inhibitors in Nonsmall Cell Lung Cancer
    Zehao Pan, Yuxian Qian, Yajing Wang, Te Zhang, Xuming Song, Hanling Ding, Rutao Li, Yijian Zhang, Zi Wang, Hui Wang, Wenjie Xia, Lei Wei, Lin Xu, Gaochao Dong, Feng Jiang
    Cancer Science.2025; 116(5): 1375.     CrossRef
  • STAT signaling in the pathogenesis and therapy of acute myeloid leukemia and myelodysplastic syndromes
    Zoe King, Sudhamsh Reddy Desai, David A. Frank, Aditi Shastri
    Neoplasia.2025; 61: 101137.     CrossRef
  • Unraveling the complexity of STAT3 in cancer: molecular understanding and drug discovery
    Yamei Hu, Zigang Dong, Kangdong Liu
    Journal of Experimental & Clinical Cancer Research.2024;[Epub]     CrossRef
  • Hepatocellular Carcinoma: Old and Emerging Therapeutic Targets
    Greta Pessino, Claudia Scotti, Maristella Maggi
    Cancers.2024; 16(5): 901.     CrossRef
  • Impact of STAT-signaling pathway on cancer-associated fibroblasts in colorectal cancer and its role in immunosuppression
    Damián Sánchez-Ramírez, Mónica G Mendoza-Rodríguez, Omar R Alemán, Fernando A Candanedo-González, Miriam Rodríguez-Sosa, Juan José Montesinos-Montesinos, Mauricio Salcedo, Ismael Brito-Toledo, Felipe Vaca-Paniagua, Luis I Terrazas
    World Journal of Gastrointestinal Oncology.2024; 16(5): 1705.     CrossRef
  • Targeted Treatment against Cancer Stem Cells in Colorectal Cancer
    Julia Martínez-Pérez, Carlos Torrado, María A. Domínguez-Cejudo, Manuel Valladares-Ayerbes
    International Journal of Molecular Sciences.2024; 25(11): 6220.     CrossRef
  • Interleukin-6 serves as a critical factor in various cancer progression and therapy
    Asma’a H. Mohamed, Abdulrahman T. Ahmed, Waleed Al Abdulmonem, Dmitry Olegovich Bokov, Alaa Shafie, Hussein Riyadh Abdul Kareem Al-Hetty, Chou-Yi Hsu, Mohammed Alissa, Shahid Nazir, Mohammad Chand Jamali, Mustafa Mudhafar
    Medical Oncology.2024;[Epub]     CrossRef
  • Targeting cytokine and chemokine signaling pathways for cancer therapy
    Ming Yi, Tianye Li, Mengke Niu, Haoxiang Zhang, Yuze Wu, Kongming Wu, Zhijun Dai
    Signal Transduction and Targeted Therapy.2024;[Epub]     CrossRef
  • Recent advances in targeted drug delivery systems for multiple myeloma
    Ashruti Pant, Aayushi Laliwala, Sarah A. Holstein, Aaron M. Mohs
    Journal of Controlled Release.2024; 376: 215.     CrossRef
  • A strategic review of STAT3 signaling inhibition by phytochemicals for cancer prevention and treatment: Advances and insights
    Suryaa Manoharan, Ekambaram Perumal
    Fitoterapia.2024; 179: 106265.     CrossRef
  • The STAT family: Key transcription factors mediating crosstalk between cancer stem cells and tumor immune microenvironment
    Mengxuan Zhu, Suyao Li, Xin Cao, Khalid Rashid, Tianshu Liu
    Seminars in Cancer Biology.2023; 88: 18.     CrossRef
  • Dual inhibition of MYC and SLC39A10 by a novel natural product STAT3 inhibitor derived from Chaetomium globosum suppresses tumor growth and metastasis in gastric cancer
    Xiaoqing Guan, Jing Yang, Weiyi Wang, Bing Zhao, Shiyu Hu, Dehua Yu, Li Yuan, Yunfu Shi, Jingli Xu, Jinyun Dong, Jinxin Wang, Xiang-Dong Cheng, Jiang-Jiang Qin
    Pharmacological Research.2023; 189: 106703.     CrossRef
  • JAK/STAT pathway: Extracellular signals, diseases, immunity, and therapeutic regimens
    Qian Hu, Qihui Bian, Dingchao Rong, Leiyun Wang, Jianan Song, Hsuan-Shun Huang, Jun Zeng, Jie Mei, Peng-Yuan Wang
    Frontiers in Bioengineering and Biotechnology.2023;[Epub]     CrossRef
  • Brevilin A is a potent anti-metastatic CRC agent that targets the VEGF-IL6-STAT3 axis in the HSCs-CRC interplay
    Xueying Fan, Mingjing Meng, Baoting Li, Hui Chen, Jincheng Tan, Keyang Xu, Shilin Xiao, Hiu-Yee Kwan, Zhongqiu Liu, Tao Su
    Journal of Translational Medicine.2023;[Epub]     CrossRef
  • Application of Nano-Antibodies for Cancer Immunotherapy
    Sunanda Singh, Samara P. Singh, Ashutosh S. Parihar
    Current Tissue Microenvironment Reports.2023; 4(2): 17.     CrossRef
  • Exploring the dynamic interplay between cancer stem cells and the tumor microenvironment: implications for novel therapeutic strategies
    Yan-Ruide Li, Ying Fang, Zibai Lyu, Yichen Zhu, Lili Yang
    Journal of Translational Medicine.2023;[Epub]     CrossRef
  • C188-9, a specific inhibitor of STAT3 signaling, prevents thermal burn-induced skeletal muscle wasting in mice
    Yuko Ono, Masafumi Saito, Kazuho Sakamoto, Yuko Maejima, Shingen Misaka, Kenju Shimomura, Nobuto Nakanishi, Shigeaki Inoue, Joji Kotani
    Frontiers in Pharmacology.2022;[Epub]     CrossRef
  • Signaling Pathways and Targeted Therapies for Stem Cells in Prostate Cancer
    Madhuvanthi Giridharan, Vasu Rupani, Satarupa Banerjee
    ACS Pharmacology & Translational Science.2022; 5(4): 193.     CrossRef
  • Insights into the role of STAT3 in intrahepatic cholangiocarcinoma (Review)
    Ranzhiqiang Yang, Yinghui Song, Kashif Shakoor, Weimin Yi, Chuang Peng, Sulai Liu
    Molecular Medicine Reports.2022;[Epub]     CrossRef
  • Inhibition of STAT3-ferroptosis negative regulatory axis suppresses tumor growth and alleviates chemoresistance in gastric cancer
    Shumin Ouyang, Huaxuan Li, Linlin Lou, Qiuyao Huang, Zhenhua Zhang, Jianshan Mo, Min Li, Jiaye Lu, Kai Zhu, Yunjie Chu, Wen Ding, Jianzheng Zhu, Ziyou Lin, Lin Zhong, Junjian Wang, Peibin Yue, James Turkson, Peiqing Liu, Yuanxiang Wang, Xiaolei Zhang
    Redox Biology.2022; 52: 102317.     CrossRef
  • Digesting the Role of JAK-STAT and Cytokine Signaling in Oral and Gastric Cancers
    Yanhong Ni, Jun T. Low, John Silke, Lorraine A. O’Reilly
    Frontiers in Immunology.2022;[Epub]     CrossRef
  • A Broad-Based Characterization of a Cell-Penetrating, Single Domain Camelid Bi-Specific Antibody Monomer That Targets STAT3 and KRAS Dependent Cancers
    Sunanda Singh, Genoveva Murillo, Justin Richner, Samara P. Singh, Erica Berleth, Vijay Kumar, Rajendra Mehta, Vijay Ramiya, Ashutosh S. Parihar
    International Journal of Molecular Sciences.2022; 23(14): 7565.     CrossRef
  • Molecular mechanisms underlying the action of carcinogens in gastric cancer with a glimpse into targeted therapy
    Elham Patrad, Solmaz Khalighfard, Taghi Amiriani, Vahid Khori, Ali Mohammad Alizadeh
    Cellular Oncology.2022; 45(6): 1073.     CrossRef
  • STAT3 and Its Targeting Inhibitors in Oral Squamous Cell Carcinoma
    Mingjing Jiang, Bo Li
    Cells.2022; 11(19): 3131.     CrossRef
  • The Role of IL-6 in Cancer Cell Invasiveness and Metastasis—Overview and Therapeutic Opportunities
    Magdalena Rašková, Lukáš Lacina, Zdeněk Kejík, Anna Venhauerová, Markéta Skaličková, Michal Kolář, Milan Jakubek, Daniel Rosel, Karel Smetana, Jan Brábek
    Cells.2022; 11(22): 3698.     CrossRef
  • An update on investigational therapies that target STAT3 for the treatment of cancer
    Matteo Santoni, Francesca Miccini, Alessia Cimadamore, Francesco Piva, Francesco Massari, Liang Cheng, Antonio Lopez-Beltran, Rodolfo Montironi, Nicola Battelli
    Expert Opinion on Investigational Drugs.2021; 30(3): 245.     CrossRef
  • RETRACTED: GATA4 Regulates Inflammation-Driven Pancreatic Ductal Adenocarcinoma Progression
    Weiliang Jiang, Congying Chen, Li Huang, Jie Shen, Lijuan Yang
    Frontiers in Cell and Developmental Biology.2021;[Epub]     CrossRef
  • Phytochemicals Targeting JAK–STAT Pathways in Inflammatory Bowel Disease: Insights from Animal Models
    Sun Young Moon, Kwang Dong Kim, Jiyun Yoo, Jeong-Hyung Lee, Cheol Hwangbo
    Molecules.2021; 26(9): 2824.     CrossRef
  • Development and Validation of an IL6/JAK/STAT3-Related Gene Signature to Predict Overall Survival in Clear Cell Renal Cell Carcinoma
    Chuanchuan Zhan, Chao Xu, Jiajun Chen, Chong Shen, Jinkun Li, Zichu Wang, Xiangrong Ying, Zhengang Luo, Yu Ren, Gangfeng Wu, Haojie Zhang, Manfei Qian
    Frontiers in Cell and Developmental Biology.2021;[Epub]     CrossRef
  • Emerging role of signal transducer and activator of transcription 3 (STAT3) in pituitary adenomas
    Cyndy Liu, Tae Nakano-Tateno, Motoyasu Satou, Constance Chik, Toru Tateno
    Endocrine Journal.2021; 68(10): 1143.     CrossRef
  • The JAK/STAT signaling pathway: from bench to clinic
    Xiaoyi Hu, Jing li, Maorong Fu, Xia Zhao, Wei Wang
    Signal Transduction and Targeted Therapy.2021;[Epub]     CrossRef
  • Interleukin-6 and colorectal cancer development
    I.А. Hromakova, P.P. Sorochan, N.E. Prokhach, I.S. Hromakova
    Український радіологічний та онкологічний журнал.2021; 29(4): 89.     CrossRef
  • Ailanthone suppresses the activity of human colorectal cancer cells through the STAT3 signaling pathway
    Haixiang Ding, Xiuchong Yu, Zhilong Yan
    International Journal of Molecular Medicine.2021;[Epub]     CrossRef
  • Radiation induces an inflammatory response that results in STAT3-dependent changes in cellular plasticity and radioresistance of breast cancer stem-like cells
    Kimberly M. Arnold, Lynn M. Opdenaker, Nicole J. Flynn, Daniel Kwesi Appeah, Jennifer Sims-Mourtada
    International Journal of Radiation Biology.2020; 96(4): 434.     CrossRef
  • Quinazoline Ligands Induce Cancer Cell Death through Selective STAT3 Inhibition and G-Quadruplex Stabilization
    Jan Jamroskovic, Mara Doimo, Karam Chand, Ikenna Obi, Rajendra Kumar, Kristoffer Brännström, Mattias Hedenström, Rabindra Nath Das, Almaz Akhunzianov, Marco Deiana, Kazutoshi Kasho, Sebastian Sulis Sato, Parham L. Pourbozorgi, James E. Mason, Paolo Medini
    Journal of the American Chemical Society.2020; 142(6): 2876.     CrossRef
  • Phosphotyrosine isosteres: past, present and future
    Robert A. Cerulli, Joshua A. Kritzer
    Organic & Biomolecular Chemistry.2020; 18(4): 583.     CrossRef
  • Anticancer activity of dietary xanthone α-mangostin against hepatocellular carcinoma by inhibition of STAT3 signaling via stabilization of SHP1
    Hai Zhang, Yu-ping Tan, Lin Zhao, Lun Wang, Nai-jie Fu, Song-ping Zheng, Xiao-fei Shen
    Cell Death & Disease.2020;[Epub]     CrossRef
  • JAK/STAT signaling in hepatocellular carcinoma
    Justin Jit Hin Tang, Dexter Kai Hao Thng, Jhin Jieh Lim, Tan Boon Toh
    Hepatic Oncology.2020;[Epub]     CrossRef
  • JAK–STAT pathway targeting for the treatment of inflammatory bowel disease
    Azucena Salas, Cristian Hernandez-Rocha, Marjolijn Duijvestein, William Faubion, Dermot McGovern, Severine Vermeire, Stefania Vetrano, Niels Vande Casteele
    Nature Reviews Gastroenterology & Hepatology.2020; 17(6): 323.     CrossRef
  • Targeting STAT3 in cancer and autoimmune diseases
    Tohid Gharibi, Zohreh Babaloo, Arezoo Hosseini, Meghdad Abdollahpour-alitappeh, Vida Hashemi, Faroogh Marofi, Kazem Nejati, Behzad Baradaran
    European Journal of Pharmacology.2020; 878: 173107.     CrossRef
  • Betacellulin drives therapy resistance in glioblastoma
    Qiwen Fan, Zhenyi An, Robyn A Wong, Xujun Luo, Edbert D Lu, Albert Baldwin, Manasi K Mayekar, Franziska Haderk, Kevan M Shokat, Trever G Bivona, William A Weiss
    Neuro-Oncology.2020; 22(4): 457.     CrossRef
  • A novel small molecule STAT3 inhibitor SLSI-1216 suppresses proliferation and tumor growth of triple-negative breast cancer cells through apoptotic induction
    Soo Kyung Park, Woong Sub Byun, Seungbeom Lee, Young Taek Han, Yoo-Seong Jeong, Kyungkuk Jang, Suk-Jae Chung, Jeeyeon Lee, Young-Ger Suh, Sang Kook Lee
    Biochemical Pharmacology.2020; 178: 114053.     CrossRef
  • STAT3 Pathway in Gastric Cancer: Signaling, Therapeutic Targeting and Future Prospects
    Milad Ashrafizadeh, Ali Zarrabi, Sima Orouei, Vahideh Zarrin, Ebrahim Rahmani Moghadam, Amirhossein Zabolian, Shima Mohammadi, Kiavash Hushmandi, Yashar Gharehaghajlou, Pooyan Makvandi, Masoud Najafi, Reza Mohammadinejad
    Biology.2020; 9(6): 126.     CrossRef
  • Towards the Inhibition of Protein–Protein Interactions (PPIs) in STAT3: Insights into a New Class of Benzothiadiazole Derivatives
    Matteo Mori, Ettore Gilardoni, Luca Regazzoni, Alessandro Pedretti, Diego Colombo, Gary Parkinson, Akira Asai, Fiorella Meneghetti, Stefania Villa, Arianna Gelain
    Molecules.2020; 25(15): 3509.     CrossRef
  • STAT3, the Challenge for Chemotherapeutic and Radiotherapeutic Efficacy
    Ping-Lian Yang, Lu-Xin Liu, En-Min Li, Li-Yan Xu
    Cancers.2020; 12(9): 2459.     CrossRef
  • Progress in Understanding the IL-6/STAT3 Pathway in Colorectal Cancer


    Yan Lin, Ziqin He, Jiazhou Ye, Ziyu Liu, Xiaomin She, Xing Gao, Rong Liang
    OncoTargets and Therapy.2020; Volume 13: 13023.     CrossRef
  • Systemic Therapy for Hepatocellular Carcinoma: Advances and Hopes
    Chen-Hao Zhang, Ming Li, You-Pei Lin, Qiang Gao
    Current Gene Therapy.2020; 20(2): 84.     CrossRef
  • Decoration of Anti-CD38 on Nanoparticles Carrying a STAT3 Inhibitor Can Improve the Therapeutic Efficacy Against Myeloma
    Yung-Hsing Huang, Mohammad Reza Vakili, Ommoleila Molavi, Yuen Morrissey, Chengsheng Wu, Igor Paiva, Amir Hasan Soleimani, Forugh Sanaee, Afsaneh Lavasanifar, Raymond Lai
    Cancers.2019; 11(2): 248.     CrossRef
  • Phase I Dose-Finding Study of OPB-111077, a Novel STAT3 Inhibitor, in Patients with Advanced Hepatocellular Carcinoma
    Changhoon Yoo, Jihoon Kang, Ho Yeong Lim, Jee Hyun Kim, Myung-Ah Lee, Kyung-Hun Lee, Tae-You Kim, Baek-Yeol Ryoo
    Cancer Research and Treatment.2019; 51(2): 510.     CrossRef
  • IL-6 signaling contributes to radioresistance of prostate cancer through key DNA repair-associated molecules ATM, ATR, and BRCA 1/2
    Xiaodong Chen, Feng Chen, Yu Ren, Guobin Weng, Lijun Xu, Xiang Xue, Peter C. Keng, Soo Ok Lee, Yuhchyau Chen
    Journal of Cancer Research and Clinical Oncology.2019; 145(6): 1471.     CrossRef
  • Proton pump inhibitor: The dual role in gastric cancer
    Moon Kyung Joo, Jong-Jae Park, Hoon Jai Chun
    World Journal of Gastroenterology.2019; 25(17): 2058.     CrossRef
  • Transcriptional Reprogramming and Novel Therapeutic Approaches for Targeting Prostate Cancer Stem Cells
    Gianluca Civenni, Domenico Albino, Dheeraj Shinde, Ramiro Vázquez, Jessica Merulla, Aleksandra Kokanovic, Sarah N. Mapelli, Giuseppina M. Carbone, Carlo V. Catapano
    Frontiers in Oncology.2019;[Epub]     CrossRef
  • STAT3 as a potential therapeutic target in triple negative breast cancer: a systematic review
    Jiang-Jiang Qin, Li Yan, Jia Zhang, Wei-Dong Zhang
    Journal of Experimental & Clinical Cancer Research.2019;[Epub]     CrossRef
  • JAK/STAT inhibition in macrophages promotes therapeutic resistance by inducing expression of protumorigenic factors
    Emily A. Irey, Chelsea M. Lassiter, Nicholas J. Brady, Pavlina Chuntova, Ying Wang, Todd P. Knutson, Christine Henzler, Thomas S. Chaffee, Rachel I. Vogel, Andrew C. Nelson, Michael A. Farrar, Kathryn L. Schwertfeger
    Proceedings of the National Academy of Sciences.2019; 116(25): 12442.     CrossRef
  • Elevated HOX gene expression in acute myeloid leukemia is associated with NPM1 mutations and poor survival
    Ádám Nagy, Ágnes Ősz, Jan Budczies, Szilvia Krizsán, Gergely Szombath, Judit Demeter, Csaba Bödör, Balázs Győrffy
    Journal of Advanced Research.2019; 20: 105.     CrossRef
  • Antitumor activity of novel pyrazole-based small molecular inhibitors of the STAT3 pathway in patient derived high grade glioma cells
    Liang Zhang, Timothy E. Peterson, Victor M. Lu, Ian F. Parney, David J. Daniels, Ilya Ulasov
    PLOS ONE.2019; 14(7): e0220569.     CrossRef
  • Inhibition of Stat3 Signaling Pathway by Natural Product Pectolinarigenin Attenuates Breast Cancer Metastasis
    Yali Li, Cailing Gan, Yange Zhang, Yan Yu, Chen Fan, Yuanle Deng, Qianyu Zhang, Xi Yu, Yiwen Zhang, Liqun Wang, Fang He, Yongmei Xie, Tinghong Ye, Wenya Yin
    Frontiers in Pharmacology.2019;[Epub]     CrossRef
  • Impact of combination therapy with anti-PD-1 blockade and a STAT3 inhibitor on the tumor-infiltrating lymphocyte status
    Tadashi Ashizawa, Akira Iizuka, Chie Maeda, Emiko Tanaka, Ryota Kondou, Haruo Miyata, Takashi Sugino, Takuya Kawata, Shoichi Deguchi, Koichi Mitsuya, Nakamasa Hayashi, Akira Asai, Mamoru Ito, Ken Yamaguchi, Yasuto Akiyama
    Immunology Letters.2019; 216: 43.     CrossRef
  • Signal Transducer and Activator of Transcription Protein 3 (STAT3): An Update on its Direct Inhibitors as Promising Anticancer Agents
    Arianna Gelain, Matteo Mori, Fiorella Meneghetti, Stefania Villa
    Current Medicinal Chemistry.2019; 26(27): 5165.     CrossRef
  • The effects of signal transducer and activator of transcription three mutations on human platelets
    Floor E. Aleva, Frank L. van de Veerdonk, Yang Li, Rahajeng N. Tunjungputri, Sami Simons, Philip G. De Groot, Mihai M. Netea, Yvonne F. Heijdra, Quirijn de Mast, André J.A.M. van der Ven
    Platelets.2018; 29(6): 602.     CrossRef
  • Mechanisms Linking Obesity and Thyroid Cancer Development and Progression in Mouse Models
    Won Gu Kim, Sheue-yann Cheng
    Hormones and Cancer.2018; 9(2): 108.     CrossRef
  • Targeting the IL-6/JAK/STAT3 signalling axis in cancer
    Daniel E. Johnson, Rachel A. O'Keefe, Jennifer R. Grandis
    Nature Reviews Clinical Oncology.2018; 15(4): 234.     CrossRef
  • Arsenic trioxide attenuates STAT-3 activity and epithelial-mesenchymal transition through induction of SHP-1 in gastric cancer cells
    Sung Ho Kim, Hyo Soon Yoo, Moon Kyung Joo, Taehyun Kim, Jong-Jae Park, Beom Jae Lee, Hoon Jai Chun, Sang Woo Lee, Young-Tae Bak
    BMC Cancer.2018;[Epub]     CrossRef
  • Linker Variation and Structure–Activity Relationship Analyses of Carboxylic Acid-based Small Molecule STAT3 Inhibitors
    Francisco Lopez-Tapia, Christine Brotherton-Pleiss, Peibin Yue, Heide Murakami, Ana Carolina Costa Araujo, Bruna Reis dos Santos, Erin Ichinotsubo, Anna Rabkin, Raj Shah, Megan Lantz, Suzie Chen, Marcus A. Tius, James Turkson
    ACS Medicinal Chemistry Letters.2018; 9(3): 250.     CrossRef
  • Decoy-Based, Targeted Inhibition of STAT3: A New Step forward for B Cell Lymphoma Immunotherapy
    Mario M. Soldevilla, Fernando Pastor
    Molecular Therapy.2018; 26(3): 675.     CrossRef
  • Two decades of research in discovery of anticancer drugs targeting STAT3, how close are we?
    Jenny D. Beebe, Jing-Yuan Liu, Jian-Ting Zhang
    Pharmacology & Therapeutics.2018; 191: 74.     CrossRef
  • Translational and clinical advances in JAK-STAT biology: The present and future of jakinibs
    Massimo Gadina, Catrina Johnson, Daniella Schwartz, Michael Bonelli, Sarfaraz Hasni, Yuka Kanno, Paul Changelian, Arian Laurence, John J O’Shea
    Journal of Leukocyte Biology.2018; 104(3): 499.     CrossRef
  • Targeting JAK-STAT signal transduction in IBD
    Christoffer Soendergaard, Fredrik Holmberg Bergenheim, Jakob Tveiten Bjerrum, Ole Haagen Nielsen
    Pharmacology & Therapeutics.2018; 192: 100.     CrossRef
  • “Do We Know Jack” About JAK? A Closer Look at JAK/STAT Signaling Pathway
    Emira Bousoik, Hamidreza Montazeri Aliabadi
    Frontiers in Oncology.2018;[Epub]     CrossRef
  • Plasticity of Type I Interferon-Mediated Responses in Cancer Therapy: From Anti-tumor Immunity to Resistance
    Megha Budhwani, Roberta Mazzieri, Riccardo Dolcetti
    Frontiers in Oncology.2018;[Epub]     CrossRef
  • STAT3 in Breast Cancer Onset and Progression: A Matter of Time and Context
    Ilenia Segatto, Gustavo Baldassarre, Barbara Belletti
    International Journal of Molecular Sciences.2018; 19(9): 2818.     CrossRef
  • Suppression of STAT3 signaling promotes cellular reprogramming into insulin-producing cells induced by defined transcription factors
    Masaki Miura, Takeshi Miyatsuka, Takehiro Katahira, Shugo Sasaki, Luka Suzuki, Miwa Himuro, Yuya Nishida, Yoshio Fujitani, Taka-aki Matsuoka, Hirotaka Watada
    EBioMedicine.2018; 36: 358.     CrossRef
  • Aptamer-iRNAs as Therapeutics for Cancer Treatment
    Mario M. Soldevilla, Daniel Meraviglia-Crivelli de Caso, Ashwathi P. Menon, Fernando Pastor
    Pharmaceuticals.2018; 11(4): 108.     CrossRef
  • A First-in-Human Phase I Study of OPB-111077, a Small-Molecule STAT3 and Oxidative Phosphorylation Inhibitor, in Patients with Advanced Cancers
    Anthony Tolcher, Keith Flaherty, Geoffrey I. Shapiro, Jordan Berlin, Thomas Witzig, Thomas Habermann, Andrea Bullock, Edwin Rock, Agnes Elekes, Chester Lin, Dusan Kostic, Naoto Ohi, Drew Rasco, Kyriakos P. Papadopoulos, Amita Patnaik, Lon Smith, Gregory M
    The Oncologist.2018; 23(6): 658.     CrossRef
  • Impact of STAT3 phosphorylation in glioblastoma stem cells radiosensitization and patient outcome
    Konstantin Masliantsev, Baptiste Pinel, Anaïs Balbous, Pierre-Olivier Guichet, Gaëlle Tachon, Serge Milin, Julie Godet, Mathilde Duchesne, Antoine Berger, Christos Petropoulos, Michel Wager, Lucie Karayan-Tapon
    Oncotarget.2018; 9(3): 3968.     CrossRef
  • Discovery of an Orally Selective Inhibitor of Signal Transducer and Activator of Transcription 3 Using Advanced Multiple Ligand Simultaneous Docking
    Wenying Yu, Chenglong Li, Wenda Zhang, Yuanzheng Xia, Shanshan Li, Jia-yuh Lin, Keqin Yu, Mu Liu, Lei Yang, Jianguang Luo, Yijun Chen, Hongbin Sun, Lingyi Kong
    Journal of Medicinal Chemistry.2017; 60(7): 2718.     CrossRef
  • Exploiting the Ref-1-APE1 node in cancer signaling and other diseases: from bench to clinic
    Fenil Shah, Derek Logsdon, Richard A. Messmann, Jill C. Fehrenbacher, Melissa L. Fishel, Mark R. Kelley
    npj Precision Oncology.2017;[Epub]     CrossRef
  • Mitochondrial dysfunction induced by a SH2 domain-targeting STAT3 inhibitor leads to metabolic synthetic lethality in cancer cells
    Davide Genini, Lara Brambilla, Erik Laurini, Jessica Merulla, Gianluca Civenni, Shusil Pandit, Rocco D'Antuono, Laurent Perez, David E. Levy, Sabrina Pricl, Giuseppina M. Carbone, Carlo V. Catapano
    Proceedings of the National Academy of Sciences.2017;[Epub]     CrossRef
  • Identification of novel small molecules that inhibit STAT3-dependent transcription and function
    Iryna Kolosenko, Yasmin Yu, Sander Busker, Matheus Dyczynski, Jianping Liu, Martin Haraldsson, Caroline Palm Apergi, Thomas Helleday, Katja Pokrovskaja Tamm, Brent D. G. Page, Dan Grander, Aamir Ahmad
    PLOS ONE.2017; 12(6): e0178844.     CrossRef
  • Antineoplastic effects of CPPTL via the ROS/JNK pathway in acute myeloid leukemia
    Hui-Er Gao, Yue Sun, Ya-Hui Ding, Jing Long, Xiao-Lei Liu, Ming Yang, Qing Ji, Ying-Hui Li, Yue Chen, Quan Zhang, Ying-Dai Gao
    Oncotarget.2017; 8(24): 38990.     CrossRef
  • Stattic and metformin inhibit brain tumor initiating cells by reducing STAT3-phosphorylation
    Verena Leidgens, Judith Proske, Lisa Rauer, Sylvia Moeckel, Kathrin Renner, Ulrich Bogdahn, Markus J. Riemenschneider, Martin Proescholdt, Arabel Vollmann-Zwerenz, Peter Hau, Corinna Seliger
    Oncotarget.2017; 8(5): 8250.     CrossRef
  • Identification of antipsychotic drug fluspirilene as a potential anti-glioma stem cell drug
    Yu Dong, Takuya Furuta, Hemragul Sabit, Tomohiro Kitabayashi, Shabierjiang Jiapaer, Masahiko Kobayashi, Yasushi Ino, Tomoki Todo, Lei Teng, Atsushi Hirao, Shi-Guang Zhao, Mitsutoshi Nakada
    Oncotarget.2017; 8(67): 111728.     CrossRef
  • Feedback Activation of STAT3 as a Cancer Drug-Resistance Mechanism
    Chengguang Zhao, Huameng Li, Huey-Jen Lin, Shulin Yang, Jiayuh Lin, Guang Liang
    Trends in Pharmacological Sciences.2016; 37(1): 47.     CrossRef
  • Targeting transcription factor STAT3 for cancer prevention and therapy
    Edna Zhi Pei Chai, Muthu K. Shanmugam, Frank Arfuso, Arunasalam Dharmarajan, Chao Wang, Alan Prem Kumar, Ramar Perumal Samy, Lina H.K. Lim, Lingzhi Wang, Boon Cher Goh, Kwang Seok Ahn, Kam Man Hui, Gautam Sethi
    Pharmacology & Therapeutics.2016; 162: 86.     CrossRef
  • Molecular Bases for Combinatorial Treatment Strategies in Patients with KRAS Mutant Lung Adenocarcinoma and Squamous Cell Lung Carcinoma
    Chiara Lazzari, Alberto Verlicchi, Anastasios Gkountakos, Sara Pilotto, Mariacarmela Santarpia, Imane Chaib, Jose Luis Ramirez Serrano, Santiago Viteri, Daniela Morales-Espinosa, Claudio Dazzi, Filippo de Marinis, Peng Cao, Niki Karachaliou, Rafael Rosell
    Pulmonary Therapy.2016; 2(1): 1.     CrossRef
  • Preclinical Characterization of 3β-(N-Acetyl l-cysteine methyl ester)-2aβ,3-dihydrogaliellalactone (GPA512), a Prodrug of a Direct STAT3 Inhibitor for the Treatment of Prostate Cancer
    Zilma Escobar, Anders Bjartell, Giacomo Canesin, Susan Evans-Axelsson, Olov Sterner, Rebecka Hellsten, Martin H Johansson
    Journal of Medicinal Chemistry.2016; 59(10): 4551.     CrossRef
  • A Positive TGF-β/c-KIT Feedback Loop Drives Tumor Progression in Advanced Primary Liver Cancer
    Andres Rojas, Pingyu Zhang, Ying Wang, Wai Chin Foo, Nina M. Muñoz, Lianchun Xiao, Jing Wang, Gregory J. Gores, Mien-Chie Hung, Boris Blechacz
    Neoplasia.2016; 18(6): 371.     CrossRef
  • Novel STAT 3 inhibitors for treating gastric cancer
    Catherine Cafferkey, Ian Chau
    Expert Opinion on Investigational Drugs.2016; 25(9): 1023.     CrossRef
  • ‘Acute myeloid leukemia: a comprehensive review and 2016 update’
    I De Kouchkovsky, M Abdul-Hay
    Blood Cancer Journal.2016; 6(7): e441.     CrossRef
  • Recent updates of precision therapy for gastric cancer: Towards optimal tailored management
    Moon Kyung Joo, Jong-Jae Park, Hoon Jai Chun
    World Journal of Gastroenterology.2016; 22(19): 4638.     CrossRef
  • Targeted inhibition of STATs and IRFs as a potential treatment strategy in cardiovascular disease
    Malgorzata Szelag, Anna Piaszyk-Borychowska, Martyna Plens-Galaska, Joanna Wesoly, Hans A.R. Bluyssen
    Oncotarget.2016; 7(30): 48788.     CrossRef
  • Cell-cell and cell-matrix adhesion in survival and metastasis: Stat3 versus Akt
    Maximilian Niit, Victoria Hoskin, Esther Carefoot, Mulu Geletu, Rozanne Arulanandam, Bruce Elliott, Leda Raptis
    Biomolecular Concepts.2015; 6(5-6): 383.     CrossRef
  • Phase 1 and pharmacological trial of OPB‐31121, a signal transducer and activator of transcription‐3 inhibitor, in patients with advanced hepatocellular carcinoma
    Takuji Okusaka, Hideki Ueno, Masafumi Ikeda, Shuichi Mitsunaga, Masato Ozaka, Hiroshi Ishii, Osamu Yokosuka, Yoshihiko Ooka, Ryo Yoshimoto, Yasuo Yanagihara, Kiwamu Okita
    Hepatology Research.2015; 45(13): 1283.     CrossRef
  • STAT3 Inhibition Enhances the Therapeutic Efficacy of Immunogenic Chemotherapy by Stimulating Type 1 Interferon Production by Cancer Cells
    Heng Yang, Takahiro Yamazaki, Federico Pietrocola, Heng Zhou, Laurence Zitvogel, Yuting Ma, Guido Kroemer
    Cancer Research.2015; 75(18): 3812.     CrossRef
  • 19,114 View
  • 258 Download
  • 98 Web of Science
  • 98 Crossref
Close layer
Phase I Study of CKD-516, a Novel Vascular Disrupting Agent, in Patients with Advanced Solid Tumors
Do-Youn Oh, Tae-Min Kim, Sae-Won Han, Dong-Yeop Shin, Yun Gyoo Lee, Keun-Wook Lee, Jee Hyun Kim, Tae-You Kim, In-Jin Jang, Jong-Seok Lee, Yung-Jue Bang
Cancer Res Treat. 2016;48(1):28-36.   Published online February 23, 2015
DOI: https://doi.org/10.4143/crt.2014.258
AbstractAbstract PDFPubReaderePub
Purpose
CKD-516 is a newly developed vascular disrupting agent. This phase I dose-escalation study of CKD-516 was conducted to determine maximum-tolerated dose (MTD), safety, pharmacokinetics, and preliminary antitumor efficacy in patients with advanced solid tumors. Materials and Methods Patients received CKD-516 intravenously on D1 and D8 every 3 weeks, in a standard 3+3 design. Safety was evaluated by National Cancer Institute Common Terminology Criteria for Adverse Events ver. 4.02 and response was assessed by Response Evaluation Criteria in Solid Tumor ver. 1.1.
Results
Twenty-three patients were treated with CKD-516 at seven dosing levels: 1 mg/m2/day (n=3), 2 mg/m2/day (n=3), 3.3 mg/m2/day (n=3), 5 mg/m2/day (n=3), 7 mg/m2/day (n=3), 9 mg/m2/day (n=6), and 12 mg/m2/day (n=2). Mean age was 54 and 56.5% of patients were male. Two dose-limiting toxicities, which were both grade 3 hypertension, were observed in two patients at 12 mg/m2/day. The MTD was determined as 12 mg/m2/day. Most common adverse events were gastrointestinal adverse events (diarrhea, 34.8% [30.4% grade 1/2, 13.0% grade 3]; nausea, 21.7% [all grade 1/2]; vomiting, 21.7% [all grade 1/2]), myalgia (17.4%, all grade 1/2), and abdominal pain (21.7% [21.7% grade 1/2, 4.3% grade 3]). The pharmacokinetic study showed the dose-linearity of all dosing levels. Among 23 patients, six patients (26.1%) showed stable disease. Median progression-free survival was 39 days (95% confidence interval, 37 to 41 days). Conclusion This study demonstrates feasibility of CKD-516, novel vascular disrupting agent, in patients with advanced solid tumor. MTD of CKD-516 was defined as 12 mg/m2/day on D1 and D8 every 3 weeks.

Citations

Citations to this article as recorded by  
  • First-in-human phase 1 study of an orally bioavailable vascular-disrupting agent DX1002 in patients with advanced solid tumors
    Xiao-Li Wei, Hao-Xiang Wu, Dan-Yun Ruan, Feng Wang, Li Xu, Yu-Hong Li, Yu-Xiang Ma, Zhi-Qiang Wang, Yun-Peng Yang, Liang-Wei Tang, Bao-Lin Chen, Zhi-Quan Yong, Rui-Hua Xu, Hong-Yun Zhao
    Cell Reports Medicine.2025; 6(2): 101969.     CrossRef
  • Natural‐Product‐Inspired Discovery of Trimethoxyphenyl‐1,2,4‐triazolosulfonamides as Potent Tubulin Polymerization Inhibitors
    Vajja Krishna Rao, Anvesh Ashtam, Dulal Panda, Sankar K. Guchhait
    ChemMedChem.2024;[Epub]     CrossRef
  • Thiazole, Isatin and Phthalimide Derivatives Tested in vivo against Cancer Models: A Literature Review of the Last Six Years
    Aline Ferreira Pinto, Janine Siqueira Nunes, José Eduardo Severino Martins, Amanda Calazans Leal, Carla Cauanny Vieira Costa Silva, Anderson José Firmino Santos da Silva, Daiane Santiago da Cruz Olímpio, Elineide Tayse Noberto da Silva, Thiers Araújo Camp
    Current Medicinal Chemistry.2024; 31(20): 2991.     CrossRef
  • CKD-516 potentiates the anti-cancer activity of docetaxel against epidermal growth factor receptor tyrosine kinase inhibitor-resistant lung cancer
    Soo Jin Kim, Kyunghyeon Lee, Jaewoo Park, Miso Park, U. Ji Kim, Se-mi Kim, Keun Ho Ryu, Keon Wook Kang
    Toxicological Research.2023; 39(1): 61.     CrossRef
  • Virulence-attenuated Salmonella engineered to secrete immunomodulators reduce tumour growth and increase survival in an autochthonous mouse model of breast cancer
    Lance B. Augustin, Liming Milbauer, Sara E. Hastings, Arnold S. Leonard, Daniel A. Saltzman, Janet L. Schottel
    Journal of Drug Targeting.2021; 29(4): 430.     CrossRef
  • A phase 1 dose-escalation and dose-expansion study to assess the safety and efficacy of CKD-516, a novel vascular disrupting agent, in combination with Irinotecan in patients with previously treated metastatic colorectal cancer
    Hyehyun Jeong, Yong Sang Hong, Jeong Eun Kim, Hyeong-Seok Lim, Joong Bae Ahn, Sang Joon Shin, Young Suk Park, Seung Tae Kim, Sae-Won Han, Tae-You Kim, Tae Won Kim
    Investigational New Drugs.2021; 39(5): 1335.     CrossRef
  • Application of triazoles as bioisosteres and linkers in the development of microtubule targeting agents
    M. Shaheer Malik, Saleh A. Ahmed, Ismail I. Althagafi, Mohammed Azam Ansari, Ahmed Kamal
    RSC Medicinal Chemistry.2020; 11(3): 327.     CrossRef
  • Tumor regression and potentiation of polymeric vascular disrupting therapy through reprogramming of a hypoxia microenvironment with temsirolimus
    Haiyang Yu, Na Shen, Yanli Bao, Li Chen, Zhaohui Tang
    Biomaterials Science.2020; 8(1): 325.     CrossRef
  • Phase I and pharmacokinetic study of the vascular‐disrupting agent CKD‐516 (NOV120401) in patients with refractory solid tumors
    Hark Kyun Kim, Jeong Won Kang, Young‐Whan Park, Jung Young Kim, Minchae Kim, Soo Jin Kim, Se‐mi Kim, Keun Ho Ryu, Seonghae Yoon, Yun Kim, Joo‐Youn Cho, Keun Seok Lee, Tak Yun, Kiwon Kim, Mi Hyang Kwak, Tae‐Sung Kim, Jinsoo Chung, Joong‐Won Park
    Pharmacology Research & Perspectives.2020;[Epub]     CrossRef
  • Revolutionizing the landscape of colorectal cancer treatment: The potential role of immune checkpoint inhibitors
    Mai F. Tolba
    International Journal of Cancer.2020; 147(11): 2996.     CrossRef
  • Discovery of tertiary amide derivatives incorporating benzothiazole moiety as anti-gastric cancer agents in vitro via inhibiting tubulin polymerization and activating the Hippo signaling pathway
    Jian Song, Qiu-Lei Gao, Bo-Wen Wu, Ting Zhu, Xin-Xin Cui, Cheng-Jun Jin, Shu-Yu Wang, Sheng-Hui Wang, Dong-Jun Fu, Hong-Min Liu, Sai-Yang Zhang, Yan-Bing Zhang, Yong-Chun Li
    European Journal of Medicinal Chemistry.2020; 203: 112618.     CrossRef
  • Anti-tumor efficacy of CKD-516 in combination with radiation in xenograft mouse model of lung squamous cell carcinoma
    Min-Young Kim, Jung-Young Shin, Jeong-Oh Kim, Kyoung-Hwa Son, Yeon Sil Kim, Chan Kwon Jung, Jin-Hyoung Kang
    BMC Cancer.2020;[Epub]     CrossRef
  • Discovery and optimization of 3,4,5-trimethoxyphenyl substituted triazolylthioacetamides as potent tubulin polymerization inhibitors
    Fang Yang, Cai-Ping He, Peng-Cheng Diao, Kwon Ho Hong, Jin-Jun Rao, Pei-Liang Zhao
    Bioorganic & Medicinal Chemistry Letters.2019; 29(1): 22.     CrossRef
  • Vascular Disrupting Agents in cancer treatment: Cardiovascular toxicity and implications for co-administration with other cancer chemotherapeutics
    Jason H. Gill, Kimberly L. Rockley, Carol De Santis, Asma K. Mohamed
    Pharmacology & Therapeutics.2019; 202: 18.     CrossRef
  • Combretastatin A4 Nanoparticles Combined with Hypoxia-Sensitive Imiquimod: A New Paradigm for the Modulation of Host Immunological Responses during Cancer Treatment
    Na Shen, Jing Wu, Chenguang Yang, Haiyang Yu, Shengcai Yang, Tete Li, Jingtao Chen, Zhaohui Tang, Xuesi Chen
    Nano Letters.2019; 19(11): 8021.     CrossRef
  • Recent advances in trimethoxyphenyl (TMP) based tubulin inhibitors targeting the colchicine binding site
    Ling Li, Sibo Jiang, Xiaoxun Li, Yao Liu, Jing Su, Jianjun Chen
    European Journal of Medicinal Chemistry.2018; 151: 482.     CrossRef
  • Combination of anti-vascular agent - DMXAA and HIF-1α inhibitor - digoxin inhibits the growth of melanoma tumors
    Ryszard Smolarczyk, Tomasz Cichoń, Ewelina Pilny, Magdalena Jarosz-Biej, Aleksandra Poczkaj, Natalia Kułach, Stanisław Szala
    Scientific Reports.2018;[Epub]     CrossRef
  • Chemoembolization with Vascular Disrupting Agent CKD-516 Dissolved in Ethiodized Oil in Combination with Doxorubicin: A VX2 Tumor Model Study
    In Joon Lee, Myungsu Lee, Soo Jin Kim, You Kyung Kim, Jong Yun Won, Jin Wook Chung
    Journal of Vascular and Interventional Radiology.2018; 29(8): 1078.     CrossRef
  • Enhanced efficacy of radiofrequency ablation for hepatocellular carcinoma using a novel vascular disrupting agent, CKD-516
    Su Jung Ham, YoonSeok Choi, Seul-I Lee, Jinil Kim, Young Il Kim, Jin Wook Chung, Kyung Won Kim
    Hepatology International.2017; 11(5): 446.     CrossRef
  • Early investigational tubulin inhibitors as novel cancer therapeutics
    Kunal Nepali, Ritu Ojha, Hsueh-Yun Lee, Jing-Ping Liou
    Expert Opinion on Investigational Drugs.2016; 25(8): 917.     CrossRef
  • Blocking Blood Flow to Solid Tumors by Destabilizing Tubulin: An Approach to Targeting Tumor Growth
    María-Jesús Pérez-Pérez, Eva-María Priego, Oskía Bueno, Maria Solange Martins, María-Dolores Canela, Sandra Liekens
    Journal of Medicinal Chemistry.2016; 59(19): 8685.     CrossRef
  • Current Advances of Tubulin Inhibitors in Nanoparticle Drug Delivery and Vascular Disruption/Angiogenesis
    Souvik Banerjee, Dong-Jin Hwang, Wei Li, Duane Miller
    Molecules.2016; 21(11): 1468.     CrossRef
  • 12,041 View
  • 140 Download
  • 22 Web of Science
  • 22 Crossref
Close layer
Regorafenib as Salvage Treatment in Korean Patients with Refractory Metastatic Colorectal Cancer
Seung Tae Kim, Tae Won Kim, Kyu-pyo Kim, Tae-You Kim, Sae-Won Han, Ji Yun Lee, Sung Hee Lim, Min-Young Lee, Haesu Kim, Young Suk Park
Cancer Res Treat. 2015;47(4):790-795.   Published online December 2, 2014
DOI: https://doi.org/10.4143/crt.2014.126
AbstractAbstract PDFPubReaderePub
Purpose
Regorafenib, an oral multi-targeted tyrosine kinase inhibitor, is considered the new standard of care in patients with chemotherapy-refractory colorectal cancers (CRCs). However, there are no data on this drug in Korean patients.
Materials and Methods
We evaluated patients who received oral regorafenib 160 mg once daily during the first 3 weeks of each 4-week cycle between August 2013 and September 2013. All patients had previously progressed fluorouracil, irinotecan, and oxaliplatin with or without biologic agents such as cetuximab or bevacizumab.
Results
Thirty-two patients were enrolled (median age, 57 years; male:female ratio, 20:12; Eastern Cooperative Oncology Group performance status [0-1:2], 31:1; colon:rectum, 21:11). The overall response rate was 3.1% and the disease control rate was 50.0% (95% confidence interval [CI]) with one partial response and 15 patients with stable disease. The median progression-free survival was 4.2 months (95% CI, 3.1 to 5.2 months) and the median overall survival has not yet been reached. The most common adverse events of grade two or higher related to regorafenib were hand-foot skin reaction (25%), mucositis (19%), abdominal pain (9%), and liver function test (LFT) abnormalities (9%). Grade 3 or 4 toxicities included LFT abnormalities (9%), abdominal pain (9%), rash (6%), anemia (3%), leukopenia (3%), neutropenic fever (3%), and fatigue (3%). There was no treatment-related death.
Conclusion
Regorafenib appears to have promising activity and tolerable toxicity profiles in Korean patients with refractory CRC, consistent with the CORRECT trial findings.

Citations

Citations to this article as recorded by  
  • Salvage Treatment Option for Metastatic Colorectal Cancer:Regorafenib
    Havva YESİL CİNKİR
    SDÜ Tıp Fakültesi Dergisi.2020; 27(4): 471.     CrossRef
  • Efficacy and safety of regorafenib in the treatment of metastatic colorectal cancer: A systematic review
    Maria Røed Skårderud, Anne Polk, Kirsten Kjeldgaard Vistisen, Finn Ole Larsen, Dorte Lisbet Nielsen
    Cancer Treatment Reviews.2018; 62: 61.     CrossRef
  • The real-world use of regorafenib for metastatic colorectal cancer: multicentre analysis of treatment pattern and outcomes in Hong Kong
    Ka-On Lam, Kin-Chung Lee, Joanne Chiu, Victor Ho-Fun Lee, Roland Leung, T S Choy, Thomas Yau
    Postgraduate Medical Journal.2017; 93(1101): 395.     CrossRef
  • Pseudocirrhosis caused by regorafenib in an advanced rectal cancer patient with multiple liver metastases
    Kensuke Kumamoto, Shungo Endo, Noriyuki Isohata, Azuma Nirei, Daiki Nemoto, Kenichi Utano, Takuro Saito, Kazutomo Togashi
    Molecular and Clinical Oncology.2017; 6(1): 63.     CrossRef
  • Incidence and risk of hematologic toxicities in cancer patients treated with regorafenib
    Bin Zhao, Hong Zhao
    Oncotarget.2017; 8(55): 93813.     CrossRef
  • Efficacy, Safety and Cost of Regorafenib in Patients with Metastatic Colorectal Cancer in French Clinical Practice
    Fabien Calcagno, Sabrina Lenoble, Zaher Lakkis, Thierry Nguyen, Samuel Limat, Christophe Borg, Marine Jary, Stefano Kim, Virginie Nerich
    Clinical Medicine Insights: Oncology.2016;[Epub]     CrossRef
  • 12,723 View
  • 149 Download
  • 13 Web of Science
  • 6 Crossref
Close layer
TGF-β Suppresses COX-2 Expression by Tristetraprolin-Mediated RNA Destabilization in A549 Human Lung Cancer Cells
Soyeong Kang, Ahrum Min, Seock-Ah Im, Sang-Hyun Song, Sang Gyun Kim, Hyun-Ah Kim, Hee-Jun Kim, Do-Youn Oh, Hyun-Soon Jong, Tae-You Kim, Yung-Jue Bang
Cancer Res Treat. 2015;47(1):101-109.   Published online October 22, 2014
DOI: https://doi.org/10.4143/crt.2013.192
AbstractAbstract PDFPubReaderePub
Purpose
Overexpression of cyclooxygenase 2 (COX-2) is thought to promote survival of transformed cells. Transforming growth factor β (TGF-β) exerts anti-proliferative effects on a broad range of epithelial cells. In the current study, we investigated whether TGF-β can regulate COX-2 expression in A549 human lung adenocarcinoma cells, which are TGF-β-responsive and overexpress COX-2.
Materials and Methods
Western blotting, Northern blotting, and mRNA stability assays were performed to demonstrate that COX-2 protein and mRNA expression were suppressed by TGF-β. We also evaluated the effects of tristetraprolin (TTP) on COX-2 mRNA using RNA interference.
Results
We demonstrated that COX-2 mRNA and protein expression were both significantly suppressed by TGF-β. An actinomycin D chase experiment demonstrated that COX-2 mRNA was more rapidly degraded in the presence of TGF-β, suggesting that TGF-β–induced inhibition of COX-2 expression is achieved via decreased mRNA stability. We also found that TGF-β rapidly and transiently induced the expression of TTP, a well-known mRNA destabilizing factor, before suppression of COX-2 mRNA expression was observed. Using RNA interference, we confirmed that increased TTP levels play a pivotal role in the destabilization of COX-2 mRNA by TGF-β. Furthermore, we showed that Smad3 is essential to TTP-dependent down-regulation of COX-2 expression in response to TGF-β.
Conclusion
The results of this study show that TGF-β down-regulated COX-2 expression via mRNA destabilization mediated by Smad3/TTP in A549 cells.

Citations

Citations to this article as recorded by  
  • Milk: A Natural Guardian for the Gut Barrier
    Yanli Wang, Yiyao Gong, Muhammad Salman Farid, Changhui Zhao
    Journal of Agricultural and Food Chemistry.2024; 72(15): 8285.     CrossRef
  • Tristetraprolin, a Potential Safeguard Against Carcinoma: Role in the Tumor Microenvironment
    Diwen Zhang, Zhigang Zhou, Ruixia Yang, Sujun Zhang, Bin Zhang, Yanxuan Tan, Lingyao Chen, Tao Li, Jian Tu
    Frontiers in Oncology.2021;[Epub]     CrossRef
  • Pan-Pim Kinase Inhibitor AZD1208 Suppresses Tumor Growth and Synergistically Interacts with Akt Inhibition in Gastric Cancer Cells
    Miso Lee, Kyung-Hun Lee, Ahrum Min, Jeongeun Kim, Seongyeong Kim, Hyemin Jang, Jee Min Lim, So Hyeon Kim, Dong-Hyeon Ha, Won Jae Jeong, Koung Jin Suh, Yae-Won Yang, Tae Yong Kim, Do-Youn Oh, Yung-Jue Bang, Seock-Ah Im
    Cancer Research and Treatment.2019; 51(2): 451.     CrossRef
  • Transforming Growth Factor β Activation Primes Canonical Wnt Signaling Through Down‐Regulation of Axin‐2
    Justin Gillespie, Rebecca L. Ross, Clarissa Corinaldesi, Filomena Esteves, Emma Derrett‐Smith, Michael F. McDermott, Gina M. Doody, Christopher P. Denton, Paul Emery, Francesco Del Galdo
    Arthritis & Rheumatology.2018; 70(6): 932.     CrossRef
  • Cyclin E overexpression confers resistance to the CDK4/6 specific inhibitor palbociclib in gastric cancer cells
    Ahrum Min, Jung Eun Kim, Yu-Jin Kim, Jee Min Lim, Seongyeong Kim, Jin Won Kim, Kyung-Hun Lee, Tae-Yong Kim, Do-Youn Oh, Yung-Jue Bang, Seock-Ah Im
    Cancer Letters.2018; 430: 123.     CrossRef
  • Identification of SMAD3 as a Novel Mediator of Inflammation in Human Myometrium In Vitro
    Martha Lappas
    Mediators of Inflammation.2018; 2018: 1.     CrossRef
  • Tristetraprolin activation by resveratrol inhibits the proliferation and metastasis of colorectal cancer cells
    Se-Ra Lee, Hua Jin, Won-Tae Kim, Won-Jung Kim, Sung Zoo Kim, Sun-Hee Leem, Soo Mi Kim
    International Journal of Oncology.2018;[Epub]     CrossRef
  • Androgen Receptor Inhibitor Enhances the Antitumor Effect of PARP Inhibitor in Breast Cancer Cells by Modulating DNA Damage Response
    Ahrum Min, Hyemin Jang, Seongyeong Kim, Kyung-Hun Lee, Debora Keunyoung Kim, Koung Jin Suh, Yaewon Yang, Paul Elvin, Mark J. O'Connor, Seock-Ah Im
    Molecular Cancer Therapeutics.2018; 17(12): 2507.     CrossRef
  • Anti‐tumor activity of the ATR inhibitor AZD6738 in HER2 positive breast cancer cells
    Hee‐Jun Kim, Ahrum Min, Seock‐Ah Im, Hyemin Jang, Kyung Hun Lee, Alan Lau, Miso Lee, Seongyeong Kim, Yaewon Yang, Jungeun Kim, Tae Yong Kim, Do‐Youn Oh, Jeffrey Brown, Mark J. O'Connor, Yung‐Jue Bang
    International Journal of Cancer.2017; 140(1): 109.     CrossRef
  • Antitumor Effect of KX-01 through Inhibiting Src Family Kinases and Mitosis
    Seongyeong Kim, Ahrum Min, Kyung-Hun Lee, Yaewon Yang, Tae-Yong Kim, Jee Min Lim, So Jung Park, Hyun-Jin Nam, Jung Eun Kim, Sang-Hyun Song, Sae-Won Han, Do-Youn Oh, Jee Hyun Kim, Tae-You Kim, David Hangauer, Johnson Yiu-Nam Lau, Kyongok Im, Dong Soon Lee,
    Cancer Research and Treatment.2017; 49(3): 643.     CrossRef
  • AZD6738, A Novel Oral Inhibitor of ATR, Induces Synthetic Lethality with ATM Deficiency in Gastric Cancer Cells
    Ahrum Min, Seock-Ah Im, Hyemin Jang, Seongyeong Kim, Miso Lee, Debora Keunyoung Kim, Yaewon Yang, Hee-Jun Kim, Kyung-Hun Lee, Jin Won Kim, Tae-Yong Kim, Do-Youn Oh, Jeff Brown, Alan Lau, Mark J. O'Connor, Yung-Jue Bang
    Molecular Cancer Therapeutics.2017; 16(4): 566.     CrossRef
  • HSP90 Inhibition Suppresses PGE2 Production via Modulating COX-2 and 15-PGDH Expression in HT-29 Colorectal Cancer Cells
    A. Mohammadi, M.M. Yaghoobi, A. Gholamhoseinian Najar, B. Kalantari-Khandani, H. Sharifi, M. Saravani
    Inflammation.2016;[Epub]     CrossRef
  • Dysregulation of TTP and HuR plays an important role in cancers
    Hao Wang, Nannan Ding, Jian Guo, Jiazeng Xia, Yulan Ruan
    Tumor Biology.2016; 37(11): 14451.     CrossRef
  • Low tristetraprolin expression promotes cell proliferation and predicts poor patients outcome in pancreatic cancer
    Zi-Ran Wei, Chao Liang, Dan Feng, Ya-Jun Cheng, Wei-Min Wang, De-Jun Yang, Yue-Xiang Wang, Qing-Ping Cai
    Oncotarget.2016; 7(14): 17737.     CrossRef
  • 13,073 View
  • 122 Download
  • 15 Web of Science
  • 14 Crossref
Close layer
Prognostic Value of Splenic Artery Invasion in Patients Undergoing Adjuvant Chemoradiotherapy after Distal Pancreatectomy for Pancreatic Adenocarcinoma
Byoung Hyuck Kim, Kyubo Kim, Eui Kyu Chie, Jin-Young Jang, Sun Whe Kim, Sae-Won Han, Do-Youn Oh, Seock-Ah Im, Tae-You Kim, Yung-Jue Bang, Ijin Joo, Sung W. Ha
Cancer Res Treat. 2015;47(2):274-281.   Published online September 12, 2014
DOI: https://doi.org/10.4143/crt.2014.025
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study was to evaluate the outcome of adjuvant chemoradiotherapy (CRT) after distal pancreatectomy (DP) in patients with pancreatic adenocarcinoma, and to identify the prognostic factors for these patients.
Materials and Methods
We performed a retrospective review of 62 consecutive patients who underwent curative DP followed by adjuvant CRT between 2000 and 2011. There were 31 men and 31 women, and the median age was 64 years (range, 38 to 80 years). Adjuvant radiotherapy was delivered to the tumor bed and regional lymph nodes with a median dose of 50.4 Gy (range, 40 to 55.8 Gy). All patients received concomitant chemotherapy, and 53 patients (85.5%) also received maintenance chemotherapy. The median follow-up period was 24 months.
Results
Forty patients (64.5%) experienced relapse. Isolated locoregional recurrence developed in 5 patients (8.1%) and distant metastasis in 35 patients (56.5%), of whom 13 had both locoregional recurrence and distant metastasis. The median overall survival (OS) and disease-free survival (DFS) were 37.5 months and 15.4 months, respectively. On multivariate analysis, splenic artery (SA) invasion (p=0.0186) and resection margin (RM) involvement (p=0.0004) were identified as significant adverse prognosticators for DFS. Also, male gender (p=0.0325) and RM involvement (p=0.0007) were associated with a significantly poor OS. Grade 3 or higher hematologic and gastrointestinal toxicities occurred in 22.6% and 4.8% of patients, respectively.
Conclusion
Adjuvant CRT may improve survival after DP for pancreatic body or tail adenocarcinoma. Our results indicated that SA invasion was a significant factor predicting inferior DFS, as was RM involvement. When SA invasion is identified preoperatively, neoadjuvant treatment may be considered.

Citations

Citations to this article as recorded by  
  • Prognostic impact of splenic vessel involvement and tumor size in distal pancreatectomy for adenocarcinoma: a retrospective multicentric cohort study
    Dominique Gantois, Théophile Guilbaud, Ugo Scemama, Edouard Girard, Olivier Picaud, Marine Lefevre, Myriam Elgani, Zeinab Hamidou, Vincent Moutardier, Paul Balandraud, Mircea Chirica, Louise Barbier, David Fuks, David Jérémie Birnbaum
    Langenbeck's Archives of Surgery.2022; 407(1): 153.     CrossRef
  • Splenic-vasculature involvement is associated with poor prognosis in resected distal pancreatic cancer
    Feng Yin, Mohammed Saad, Jingmei Lin, Christopher R Jackson, Bing Ren, Cynthia Lawson, Dipti M Karamchandani, Belen Quereda Bernabeu, Wei Jiang, Teena Dhir, Richard Zheng, Christopher W Schultz, Dongwei Zhang, Courtney L Thomas, Xuchen Zhang, Jinping Lai,
    Gastroenterology Report.2021; 9(2): 139.     CrossRef
  • Meta-analysis of recurrence pattern after resection for pancreatic cancer
    M Tanaka, A L Mihaljevic, P Probst, M Heckler, U Klaiber, U Heger, M W Büchler, T Hackert
    British Journal of Surgery.2019; 106(12): 1590.     CrossRef
  • Improved Survival in Patients with Resected Pancreatic Carcinoma Using Postoperative Intensity-Modulated Radiotherapy and Regional Intra-Arterial Infusion Chemotherapy
    Ningyi Ma, Zheng Wang, Jiandong Zhao, Jiang Long, Jin Xu, Zhigang Ren, Guoliang Jiang
    Medical Science Monitor.2017; 23: 2315.     CrossRef
  • Role of Adjuvant Radiotherapy in Left-Sided Pancreatic Cancer—Population-Based Analysis with Propensity Score Matching
    Yu Jin Lim, Kyubo Kim, Eui Kyu Chie, BoKyong Kim, Sung W. Ha
    Journal of Gastrointestinal Surgery.2015; 19(12): 2183.     CrossRef
  • 12,173 View
  • 93 Download
  • 6 Web of Science
  • 5 Crossref
Close layer

Cancer Res Treat : Cancer Research and Treatment
Close layer
TOP