Cancer Research and Treatment

Original Articles

Lung and Thoracic cancer

Factors Associated with Postoperative Recurrence in Stage I to IIIA Non–Small Cell Lung Cancer with Epidermal Growth Factor Receptor Mutation: Analysis of Korean National Population Data: Kyu Yean Kim, Ho Cheol Kim, Tae Jung Kim, Hong Kwan Kim, Mi Hyung Moon, Kyongmin Sarah Beck, Yang Gun Suh, Chang Hoon Song, Jin Seok Ahn, Jeong Eun Lee, Jae Hyun Jeon, Chi Young Jung, Jeong Su Cho, Yoo Duk Choi, Seung Sik Hwang, Chang Min Choi, Seung Hun Jang, Jeong Uk Lim, Korean Association for Lung Cancer, Korea Central Cancer Registry; Cancer Res Treat. 2025;57(1):83-94. Published online July 10, 2024; DOI: https://doi.org/10.4143/crt.2024.073

Abstract PDF Supplementary Material PubReader ePub: Purpose
Recent development in perioperative treatment of resectable non–small cell lung cancer (NSCLC) have changed the landscape of early lung cancer management. The ADAURA trial has demonstrated the efficacy of adjuvant osimertinib treatment in resectable NSCLC patients; however, studies are required to show which subgroup of patients are at a high risk of relapse and require adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor treatment. This study evaluated risk factors for postoperative relapse among patients who underwent complete resection.
Materials and Methods
Data were obtained from the Korean Association for Lung Cancer Registry (KALC-R), a database created using a retrospective sampling survey by the Korean Central Cancer Registry (KCCR) and the Lung Cancer Registration Committee.
Results
A total of 3,176 patients who underwent curative resection was evaluated. The mean observation time was approximately 35.4 months. Among stage I to IIIA NSCLC patients, the EGFR-mutant subgroup included 867 patients, and 75.2%, 11.2%, and 11.8% were classified as stage I, stage II, and stage III, respectively. Within the EGFR-mutant subgroup, 44 (5.1%) and 121 (14.0%) patients showed early and late recurrence, respectively. Multivariate analysis on association with postoperative relapse among the EGFR-mutant subgroup showed that age, pathologic N and TNM stages, pleural invasion status, and surgery type were independent significant factors.
Conclusion
Among the population that underwent complete resection for early NSCLC with EGFR mutation, patients with advanced stage, pleural invasion, or limited resection are more likely to show postoperative relapse.

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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

Abstract PDF Supplementary Material PubReader ePub

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.

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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

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Lung and Thoracic cancer

Targeting CD73 to Overcomes Resistance to First-Generation EGFR Tyrosine Kinase Inhibitors in Non–Small Cell Lung Cancer: Miso Kim, Soyeon Kim, Jeemin Yim, Bhumsuk Keam, Tae Min Kim, Yoon Kyung Jeon, Dong-Wan Kim, Dae Seog Heo; Cancer Res Treat. 2023;55(4):1134-1143. Published online May 23, 2023; DOI: https://doi.org/10.4143/crt.2023.311

Abstract PDF Supplementary Material PubReader ePub

Purpose
In patients with epidermal growth factor receptor (EGFR)-mutant non–small cell lung cancer (NSCLC), EGFR tyrosine kinase inhibitors (TKIs) improve response rate and survival. However, most patients eventually develop resistance. This study aimed to identify the role of CD73 in EGFR-mutant NSCLC and explore whether CD73 inhibition may serve as a therapeutic strategy in NSCLC patients with acquired resistance to EGFR-TKIs.
Materials and Methods
We evaluated the prognostic role of CD73 expression in EGFR-mutant NSCLC using tumor samples from a single institution. We silenced CD73 in EGFR-TKI–resistant cell lines using short hairpin RNA (shRNA) targeting CD73 and also transfected a vector alone as a negative control. Using these cell lines, cell proliferation and viability assays, immunoblot assays, cell cycle analysis, colony-forming assays, flow cytometry, and apoptosis analysis were performed.
Results
High expression of CD73 was associated with shorter survival in patients with metastatic EGFR-mutant NSCLC treated with first-generation EGFR-TKI. CD73 inhibition synergistically inhibited cell viability with first-generation EGFR-TKI treatment compared with the negative control. When CD73 inhibition and EGFR-TKI treatment were combined, G0/G1 cell cycle arrest was induced through the regulation of p21 and cyclin D1. In addition, the apoptosis rate was increased in CD73 shRNA-transfected cells treated with EGFR-TKI.
Conclusion
High expression of CD73 adversely affects the survival of patients with EGFR-mutant NSCLC. The study demonstrated that inhibiting CD73 in EGFR-TKI–resistant cell lines resulted in increased apoptosis and cell cycle arrest, which overcame the acquired resistance to first-generation EGFR-TKIs. Further research is needed to determine whether blocking CD73 plays a therapeutic role in EGFR-TKI–resistant patients with EGFR-mutant NSCLC.

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Simultaneous blockade of the CD73/EGFR axis inhibits tumor growth
Keivan Ardeshiri, Hadi Hassannia, Ghasem Ghalamfarsa, Hanieh Jafary, Farhad Jadidi
IUBMB Life.2025;[Epub] CrossRef
Comprehensive pan-cancer analysis of CD73: Explore its association with prognosis and tumor immune microenvironment
Chen Chen, Sasa Liu, Yanfen Ma
Heliyon.2024; 10(22): e40329. CrossRef

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Final Report on Real-World Effectiveness of Sequential Afatinib and Osimertinib in EGFR-Positive Advanced Non–Small Cell Lung Cancer: Updated Analysis of the RESET Study: Taeyun Kim, Tae Won Jang, Chang Min Choi, Mi-Hyun Kim, Sung Yong Lee, Yoon Soo Chang, Kye Young Lee, Seung Joon Kim, Sei Hoon Yang, Jeong Seon Ryu, Jeong Eun Lee, Shin Yup Lee, Chan Kwon Park, Sang Hoon Lee, Seung Hun Jang, Seong Hoon Yoon, Hyung-Joo Oh; Cancer Res Treat. 2023;55(4):1152-1170. Published online May 19, 2023; DOI: https://doi.org/10.4143/crt.2023.493

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to report the final analysis of time-on-treatment (TOT) and overall survival (OS) in patients with advanced-stage epidermal growth factor receptor (EGFR)+ non–small cell lung cancer (NSCLC) who received sequential afatinib and osimertinib and to compare the outcomes with other second-line regimens (comparator group).
Materials and Methods
In this updated report, the existing medical records were reviewed and rechecked. TOT and OS were updated and analyzed according to clinical features using the Kaplan-Meier method and log-rank test. TOT and OS were compared with those of the comparator group, in which most patients received pemetrexed-based treatments. A multivariable Cox proportional hazard model was used to evaluate features that could affect survival outcomes.
Results
The median observation time was 31.0 months. The follow-up period was extended to 20 months. A total of 401 patients who received first-line afatinib were analyzed (166 with T790M+ and second-line osimertinib, and 235 with unproven T790M and other second-line agents). Median TOTs on afatinib and osimertinib were 15.0 months (95% confidence interval [CI], 14.0 to 16.1) and 11.9 months (95% CI, 8.9 to 14.6), respectively. The median OS in the osimertinib group was 54.3 months (95% CI, 46.7 to 61.9), much longer than that in the comparator group. In patients who received osimertinib, the OS was longest with Del19+ (median, 59.1; 95% CI, 48.7 to 69.5).
Conclusion
This is one of the largest real-world studies reporting the encouraging activity of sequential afatinib and osimertinib in Asian patients with EGFR+ NSCLC who acquired the T790M mutation, particularly Del19+.

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KEAP1-NRF2 Pathway as a Novel Therapeutic Target for EGFR-Mutant Non-small Cell Lung Cancer
Jae-Sun Choi, Hye-Min Kang, Kiyong Na, Jiwon Kim, Tae-Woo Kim, Junyang Jung, Heejin Lim, Hyewon Seo, Seung Hyeun Lee
Tuberculosis and Respiratory Diseases.2025; 88(1): 138. CrossRef
A real-world cohort study of first-line afatinib in patients with EGFR-mutant advanced non-small cell lung cancer in Vietnam
Cam Phuong Pham, Thi Thai Hoa Nguyen, Anh Tu Do, Tuan Khoi Nguyen, Thi Anh Thu Hoang, Tuan Anh Le, Dinh Thy Hao Vuong, Dac Nhan Tam Nguyen, Van Khiem Dang, Thi Oanh Nguyen, Van Luan Pham, Minh Hai Nguyen, Thi Huyen Trang Vo, Hung Kien Do, Ha Thanh Vu, Thi
BMC Cancer.2024;[Epub] CrossRef
Real‐world evidence of brigatinib as second‐line treatment after crizotinib for ALK+ non‐small cell lung cancer using South Korean claims data (K‐AREAL)
Jeong Eun Lee, Jin Hyun Nam, Sun Hong Kwon, Bo Kyung Kim, Seung Min Ha
Cancer Medicine.2024;[Epub] CrossRef
Serum Concentrations of IGF-1R, ERK2, and EGFR and Their Clinical Significance in Patients with Neuroendocrine Tumors
Roksana Duszkiewicz, Janusz Strzelczyk, Elżbieta Chełmecka, Joanna Katarzyna Strzelczyk
Applied Sciences.2024; 14(16): 6998. CrossRef
Optimal first-line treatment for EGFR-mutated NSCLC: a comparative analysis of osimertinib and second-generation EGFR-TKIs
Hsu-Yuan Chen, Chia-Hung Chen, Wei-Chih Liao, Yu-Chao Lin, Hung-Jen Chen, Te-Chun Hsia, Wen-Chien Cheng, Chih-Yen Tu
BMC Pulmonary Medicine.2024;[Epub] CrossRef
Osimertinib as Second- and ≥Third-Line Treatment in Advanced and Recurrence EGFR-Mutant NSCLC Patients Harboring Acquired T790M Mutation
Mu-Han Peng, Yen-Hsiang Huang, Kuo-Hsuan Hsu, Jeng-Sen Tseng, Po-Hsin Lee, Kun-Chieh Chen, Gee-Chen Chang, Tsung-Ying Yang
Cancers.2024; 16(24): 4174. CrossRef
Effectiveness of first-line anticancer treatment may predict treatment response in further lines in stage III/IV patients with non-small cell lung cancer
Monika Bratova, Jana Skrickova, Magda Matusikova, Karolina Hrabcova, Libor Havel, Leona Koubkova, Michal Hrnciarik, Jana Krejci, Ondrej Fischer, Martin Svaton, Kristian Brat
Journal of Cancer Research and Clinical Oncology.2023; 149(19): 17123. CrossRef

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Should We Perform Repeated Re-biopsy for the Detection of T790M Mutation?: Saerom Kim, Soo Han Kim, Jinmi Kim, Mi-Hyun Kim, Min Ki Lee, Jung Seop Eom; Cancer Res Treat. 2023;55(4):1190-1197. Published online April 17, 2023; DOI: https://doi.org/10.4143/crt.2023.320

Abstract PDF PubReader ePub

Purpose
Epidermal growth factor receptor (EGFR) T790M mutations have been detected in the second or third rebiopsy, even if the T790M mutation was not identified in the first rebiopsy. This meta-analysis investigated the EGFR T790M mutation detection rates and its additional advantages with repeated rebiopsies.
Materials and Methods
We searched through the PubMed and EMBASE databases up to June 2022. Studies reporting rebiopsy to identify the EGFR T790M mutation in case of disease progression among patients with advanced non-small cell lung cancer and multiple rebiopsies were included. The quality of the included studies was checked using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool.
Results
Eight studies meeting the eligibility criteria, reporting 1,031 EGFR mutation–positive patients were selected. The pooled EGFR T790M mutation detection rate of the first and repeated rebiopsies were 0.442 (95% confidence interval [CI], 0.411 to 0.473; I²=84%; p < 0.01) and 0.465 (95% CI, 0.400 to 0.530; I²=69%; p < 0.01), respectively. Overall, the pooled detection rate of EGFR T790M mutation was 0.545 (95% CI, 0.513 to 0.576), which increased by 10.3% with repeated rebiopsies.
Conclusion
This meta-analysis identified that repeated rebiopsy increases the detection rate of EGFR T790M mutation by 10.3%, even if EGFR T790M mutation is not detected in the first rebiopsy. Our results indicate that the spatiotemporal T790M heterogeneity can be overcome with repeated rebiopsy.

Citations

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Clinical utility of repeated rebiopsy for EGFR T790M mutation detection in non-small cell lung cancer
Eun Hye Lee, Se Hyun Kwak, Kyeong Yeon Kim, Chi Young Kim, Sang Hoon Lee, Seok-Jae Heo, Yoon Soo Chang, Eun Young Kim
Frontiers in Oncology.2024;[Epub] CrossRef
Repeated rebiopsy for detection of EGFR T790M mutation in patients with advanced-stage lung adenocarcinoma: Associated factors and treatment outcomes of Osimertinib
Taeyun Kim, Junsu Choe, Sun Hye Shin, Byeong-Ho Jeong, Kyungjong Lee, Hojoong Kim, Se-Hoon Lee, Sang-Won Um, Hamidreza Montazeri Aliabadi
PLOS ONE.2024; 19(9): e0310079. CrossRef
Rebiopsie tumorale : quand ? pour qui ? pourquoi ? comment ?
V. Fallet
Revue des Maladies Respiratoires Actualités.2023; 15(2): 2S121. CrossRef

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The Role of Brain Radiotherapy before First-Line Afatinib Therapy, Compared to Gefitinib or Erlotinib, in Patients with EGFR-Mutant Non–Small Cell Lung Cancer: Hyun Ae Jung, Sehhoon Park, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn, Jong-Mu Sun; Cancer Res Treat. 2023;55(2):479-487. Published online December 27, 2022; DOI: https://doi.org/10.4143/crt.2022.1344

Abstract PDF Supplementary Material PubReader ePub

Purpose
Brain metastasis is common in patients with epidermal growth factor receptor (EGFR)–mutant non–small cell lung cancer (NSCLC) at initial presentation. A previous study showed that brain radiotherapy (RT) before first-generation (first-G) EGFR–tyrosine kinase inhibitor (TKI) therapy is associated with longer overall survival than TKI therapy alone. However, there is no data regarding the role of additional brain RT before afatinib therapy.
Materials and Methods
Between October 2014 and June 2019, EGFR-mutant NSCLC patients with brain metastases who started first-G EGFR-TKIs (gefitinib or erlotinib) or afatinib as first-line therapy were retrospectively analyzed. This study compared overall survival and intracranial progression-free survival (PFS) between patients who received EGFR-TKIs alone and EGFR-TKIs with brain RT and either a first-G EGFR-TKI or afatinib, respectively.
Results
The median follow-up duration was 29.6 months (range, 1.5 to 116.9 months). In the first-G EGFR-TKI group (n=155), 94 patients (60.6%) received the first-G EGFR-TKI alone and 61 patients (39.4%) received brain RT prior to their first-G EGFR-TKI. In the afatinib group (n=204), 126 patients (61.8%) received afatinib alone and 78 patients (38.2%) received brain RT prior to afatinib. There was no difference in overall survival rates between the groups with RT (35.6 months: 95% confidence interval [CI], 27.9 to 43.3) and without RT (31.4 months: 95% CI, 23.9 to 38.9) in the afatinib group (p=0.58), but there was a significant difference in overall survival in the first-G EGFR-TKI group in a manner favoring additional brain RT (41.1 months: 95% CI, 30.5 to 51.7 vs. 25.8 months: 95% CI, 20.1 to 31.5; p=0.02). Meanwhile, median intracranial PFS was not different between patients who received EGFR-TKI therapy alone vs. EGFR-TKI therapy with brain RT in both the first-G EGFR-TKI (p=0.39) and afatinib (p=0.24) groups.
Conclusion
Afatinib therapy alone showed comparable survival outcomes to those of afatinib with brain RT. The current study suggests that brain RT could be an optional, not mandatory, treatment modality when afatinib therapy is considered in patients with EGFR-mutant NSCLC.

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Radiation Recall Pneumonitis: The Open Challenge in Differential Diagnosis of Pneumonia Induced by Oncological Treatments
Francesca Grassi, Vincenza Granata, Roberta Fusco, Federica De Muzio, Carmen Cutolo, Michela Gabelloni, Alessandra Borgheresi, Ginevra Danti, Carmine Picone, Andrea Giovagnoni, Vittorio Miele, Nicoletta Gandolfo, Antonio Barile, Valerio Nardone, Roberta G
Journal of Clinical Medicine.2023; 12(4): 1442. CrossRef
Dacomitinib in EGFR-mutant non-small-cell lung cancer with brain metastasis: a single-arm, phase II study
H.A. Jung, S. Park, S.-H. Lee, J.S. Ahn, M.-J. Ahn, J.-M. Sun
ESMO Open.2023; 8(6): 102068. CrossRef
Recent advances progress of targeted drugs combined with radiotherapy for advanced non-small cell lung cancer: a review
Jiamin Xu, Zhongming Wang
Frontiers in Oncology.2023;[Epub] CrossRef

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The Clinical Outcomes of Different First-Line EGFR-TKIs Plus Bevacizumab in Advanced EGFR-Mutant Lung Adenocarcinoma: Yen-Hsiang Huang, Kuo-Hsuan Hsu, Chun-Shih Chin, Jeng-Sen Tseng, Tsung-Ying Yang, Kun-Chieh Chen, Kang-Yi Su, Sung-Liang Yu, Jeremy J.W. Chen, Gee-Chen Chang; Cancer Res Treat. 2022;54(2):434-444. Published online August 2, 2021; DOI: https://doi.org/10.4143/crt.2021.671

Abstract PDF PubReader ePub

Purpose
The aim of this study was to investigate the efficacy of various epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitors (TKIs) plus bevacizumab in advanced EGFR-mutant lung adenocarcinoma patients.
Materials and Methods
From August 2016 to October 2020, we enrolled advanced lung adenocarcinoma patients harboring exon 19 deletion or L858R receiving gefitinib, erlotinib and afatinib plus bevacizumab as the first-line treatment for the purposes of analysis.
Results
A total of 36 patients were included in the final analysis. Three patients received gefitinib, 17 received erlotinib, and 16 received afatinib combined with bevacizumab as the first-line treatment. The objective response rate was 77.8%, and disease control rate was 94.4%. The overall median progression-free survival (PFS) was 16.4 months, while the median PFS was 17.1 months in patients with exon 19 deletion, and 16.2 months in patients with L858R mutation (p=0.311). Regarding the use of different EGFR-TKIs, the median PFS was 17.1 months in the erlotinib group and 21.6 months in the afatinib group (p=0.617). In patients with brain metastasis at baseline, the median PFS was 18.9 months in the erlotinib group and 16.4 months in the afatinib group (p=0.747). Amongst patients harboring exon 19 deletion, the median PFS was 16.2 months in the erlotinib group and not-reached in the afatinib group (p=0.141). In patients with L858R mutation, the median PFS was 18.9 months in the erlotinib group and 16.2 months in the afatinib group (p=0.481).
Conclusion
Our research demonstrates that not only erlotinib combined with bevacizumab, but also afatinib plus bevacizumab as first-line treatment, provides solid clinical efficacy in advanced EGFR-mutant lung adenocarcinoma patients.

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Clinical outcome of bevacizumab or ramucirumab combined with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors as the first line therapy in susceptible EGFR‐mutated advanced non‐small‐cell lung
Chia‐Yu Kuo, Ming‐Ju Tsai, Jen‐Yu Hung, Mei‐Hsuan Lee, Kuan‐Li Wu, Yu‐Chen Tsai, Cheng‐Hao Chuang, Chung‐Wen Huang, Chin‐Ling Chen, Chih‐Jen Yang, Inn‐Wen Chong
The Kaohsiung Journal of Medical Sciences.2024; 40(5): 467. CrossRef
Scorpiones, Scolopendra and Gekko Inhibit Lung Cancer Growth and Metastasis by Ameliorating Hypoxic Tumor Microenvironment via PI3K/AKT/mTOR/HIF-1α Signaling Pathway
Qi-yuan Mao, Xue-qian Wang, Fei Lin, Ming-wei Yu, Hui-ting Fan, Qi Zheng, Lan-chun Liu, Chu-chu Zhang, Dao-rui Li, Hong-sheng Lin
Chinese Journal of Integrative Medicine.2024; 30(9): 799. CrossRef
Real-world clinical efficacy of bevacizumab biosimilar in patients with advanced non-small-cell lung cancer
Wei-Fan Ou, Kuo-Hsuan Hsu, Jeng-Sen Tseng, Po-Hsin Lee, Kun-Chieh Chen, Yen-Hsiang Huang, Gee-Chen Chang, Tsung-Ying Yang
Therapeutic Advances in Medical Oncology.2024;[Epub] CrossRef
Bevacizumab plus erlotinib versus erlotinib alone for advanced EGFR-mutant non-small cell lung cancer: a meta-analysis of randomized clinical trials
Ruijian Li, Weiyi Li, Fang Zhang, Shanshan Li
European Journal of Medical Research.2023;[Epub] CrossRef
Bevacizumab versus Ramucirumab in EGFR-Mutated Metastatic Non-Small-Cell Lung Cancer Patients: A Real-World Observational Study
Wen-Chien Cheng, Yi-Cheng Shen, Chieh-Lung Chen, Wei-Chih Liao, Chia-Hung Chen, Hung-Jen Chen, Chih-Yen Tu, Te-Chun Hsia
Cancers.2023; 15(3): 642. CrossRef
Afatinib/bevacizumab/erlotinib

Reactions Weekly.2023; 1952(1): 32. CrossRef
Comprehensive analysis of prediction of the EGFR mutation and subtypes based on the spinal metastasis from primary lung adenocarcinoma
Ran Cao, Huanhuan Chen, Huan Wang, Yan Wang, E-Nuo Cui, Wenyan Jiang
Frontiers in Oncology.2023;[Epub] CrossRef
When to add anti-angiogenesis drugs to EGFR-mutated metastatic non–small cell lung cancer patients: a real-world study from Taiwan
Chieh-Lung Chen, Sing-Ting Wang, Wei-Chih Liao, Chia-Hung Chen, Chih-Yen Tu, Hung-Jen Chen, Te-Chun Hsia, Wen-Chien Cheng
BMC Cancer.2022;[Epub] CrossRef
State-of-the-Art Molecular Oncology of Lung Cancer in Taiwan
Yung-Hung Luo, Kung-Hao Liang, Hsu-Ching Huang, Chia-I Shen, Chi-Lu Chiang, Mong-Lien Wang, Shih-Hwa Chiou, Yuh-Min Chen
International Journal of Molecular Sciences.2022; 23(13): 7037. CrossRef
Comparison of afatinib and erlotinib combined with bevacizumab in untreated stage IIIB/IV epidermal growth factor receptor-mutated lung adenocarcinoma patients: a multicenter clinical analysis study
Suey-Haur Lee, Yu-Ching Lin, Li-Chung Chiu, Jia-Shiuan Ju, Pi-Hung Tung, Allen Chung-Cheng Huang, Shih-Hong Li, Yueh-Fu Fang, Chih-Hung Chen, Scott Chih-Hsi Kuo, Chin-Chou Wang, Cheng-Ta Yang, Ping-Chih Hsu
Therapeutic Advances in Medical Oncology.2022;[Epub] CrossRef
The efficacy and tolerability of combining pemetrexed-based chemotherapy with gefitinib in the first-line treatment of non-small cell lung cancer with mutated EGFR: A pooled analysis of randomized clinical trials
Bi-Cheng Wang, Wen-Xuan Zhang, Bo-Hua Kuang, Guo-He Lin, Alessandro Rizzo
PLOS ONE.2022; 17(10): e0275919. CrossRef

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Gastrointestinal cancer

Effect of Combining EGFR Tyrosine Kinase Inhibitors and Cytotoxic Agents on Cholangiocarcinoma Cells: Boonyakorn Boonsri, Kiren Yacqub-Usman, Pakpoom Thintharua, Kyaw Zwar Myint, Thannicha Sae-Lao, Pam Collier, Chinnawut Suriyonplengsaeng, Noppadol Larbcharoensub, Brinda Balasubramanian, Simran Venkatraman, Isioma U. Egbuniwe, Dhanwant Gomez, Abhik Mukherjee, Supeecha Kumkate, Tavan Janvilisri, Abed M Zaitoun, Thiti Kuakpaetoon, Rutaiwan Tohtong, Anna M Grabowska, David O. Bates, Kanokpan Wongprasert; Cancer Res Treat. 2021;53(2):457-470. Published online October 7, 2020; DOI: https://doi.org/10.4143/crt.2020.585

Abstract PDF Supplementary Material PubReader ePub

Purpose
The potential of members of the epidermal growth factor receptor (ErbB) family as drug targets in cholangiocarcinoma (CCA) has not been extensively addressed. Although phase III clinical trials showed no survival benefits of erlotinib in patients with advanced CCA, the outcome of the standard-of-care chemotherapy treatment for CCA, gemcitabine/cisplatin, is discouraging so we determined the effect of other ErbB receptor inhibitors alone or in conjunction with chemotherapy in CCA cells. Materials and Methods ErbB receptor expression was determined in CCA patient tissues by immunohistochemistry and digital-droplet polymerase chain reaction, and in primary cells and cell lines by immunoblot. Effects on cell viability and cell cycle distribution of combination therapy using ErbB inhibitors with chemotherapeutic drugs was carried out in CCA cell lines. 3D culture of primary CCA cells was then adopted to evaluate the drug effect in a setting that more closely resembles in vivo cell environments.
Results
CCA tumors showed higher expression of all ErbB receptors compared with resection margins. Primary and CCA cell lines had variable expression of erbB receptors. CCA cell lines showed decreased cell viability when treated with chemotherapeutic drugs (gemcitabine and 5-fluorouracil) but also with ErbB inhibitors, particularly afatinib, and with a combination. Sequential treatment of gemcitabine with afatinib was particularly effective. Co-culture of CCA primary cells with cancer-associated fibroblasts decreased sensitivity to chemotherapies, but sensitized to afatinib. Conclusion Afatinib is a potential epidermal growth factor receptor targeted drug for CCA treatment and sequential treatment schedule of gemcitabine and afatinib could be explored in CCA patients.

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Rational synthesis and evaluation of 2,4-diamino-thieno[2,3-d]pyrimidines as antitumor agents
Yumeng Gao, Ainv Zhang, Li Li, Fengxu Wu, Yanggen Hu
Journal of Saudi Chemical Society.2024; 28(1): 101794. CrossRef
Identification and validation of a novel ferroptosis-related gene signature for prognosis and potential therapeutic target prediction in cholangiocarcinoma
Apiwit Sae-fung, Apiwat Mutirangura, Siriporn Jitkaew
Frontiers in Immunology.2023;[Epub] CrossRef
Preclinical evidence for anaplastic lymphoma kinase inhibitors as novel therapeutic treatments for cholangiocarcinoma
Kyaw Zwar Myint, Mireia Sueca-Comes, Pamela Collier, Brinda Balasubramanian, Simran Venkatraman, John Gordan, Abed M. Zaitoun, Abhik Mukherjee, Arvind Arora, Noppadol Larbcharoensub, Chinnawut Suriyonplengsaeng, Kanokpan Wongprasert, Tavan Janvilisri, Dha
Frontiers in Oncology.2023;[Epub] CrossRef
CP-673451, a Selective Platelet-Derived Growth Factor Receptor Tyrosine Kinase Inhibitor, Induces Apoptosis in Opisthorchis viverrini-Associated Cholangiocarcinoma via Nrf2 Suppression and Enhanced ROS
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Lactic acidosis promotes aggressive features of cholangiocarcinoma cells via upregulating ALDH1A3 expression through EGFR axis
Ubonrat Thamrongwaranggoon, Marutpong Detarya, Wunchana Seubwai, Charupong Saengboonmee, Shinjiro Hino, Tomoaki Koga, Mitsuyoshi Nakao, Sopit Wongkham
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Advances of cancer-associated fibroblasts in liver cancer
Hao Peng, Erwei Zhu, Yewei Zhang
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Case Report

EGFR C797S as a Resistance Mechanism of Lazertinib in Non-small Cell Lung Cancer with EGFR T790M Mutation: Sehhoon Park, Bo Mi Ku, Hyun Ae Jung, Jong-Mu Sun, Jin Seok Ahn, Se-Hoon Lee, Keunchil Park, Myung-Ju Ahn; Cancer Res Treat. 2020;52(4):1288-1290. Published online June 22, 2020; DOI: https://doi.org/10.4143/crt.2020.278

Abstract PDF PubReader ePub

The non-small cell lung cancer with activating epidermal growth factor receptor (EGFR) mutation eventually acquires resistant to either first or second-generation EGFR tyrosine kinase inhibitor (TKI). As the following option, targeting EGFR T790M with third-generation EGFR TKI is now established as a standard treatment option. In this study, we are reporting the first case of resistance mechanism to the novel third-generation EGFR TKI, lazertinib, which showed promising clinical efficacy in phase 1-2 study. The patients showed resistance to the treatment by acquiring the additional EGFR C797S mutation in cis which is also confirmed from the patient-derived cell lines.

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