Cancer Research and Treatment

Original Articles

Hematologic malignancy

A Phase II Study to Evaluate the Efficacy of Bortezomib in Combination with Thalidomide in Treatment-Naïve Waldenstrom Macroglobulinemia Patients: Ja Min Byun, Junghoon Shin, Sang-A Kim, Hyunkyung Park, Jiyun Lee, Dong-Yeop Shin, Junshik Hong, Jeong-Ok Lee, Soo-Mee Bang, Inho Kim, Sung-Soon Yoon, Youngil Koh; Cancer Res Treat. 2024;56(2):675-680. Published online September 25, 2023; DOI: https://doi.org/10.4143/crt.2023.681

Abstract PDF PubReader ePub: Purpose
Despite the recent success of Bruton’s tyrosine kinase (BTK) inhibitors for the treatment of Waldenstrom macroglobulinemia (WM), their indefinite treatment duration ultimately tantamount to substantial financial and emotional burden. On the other hand, fixed duration of proteasome inhibitors (PI) have shown rapid and reasonable response in WM treatment. Despite the well-known synergism between PI and immunomodulatory drugs (IMiD), there is no trials evaluating such combination in WM.
Materials and Methods
Based on above, we designed this phase II study to investigate the efficacy and safety of 6 cycles of 28-day bortezomib-thalidomide-dexamethasone (VTD) regimen for treatment-naïve WM.
Results
A total of 15 patients were enrolled: major response rate was 64.3%, and overall response rate was 78.6%. During the median follow-up of 41 months, median progression-free survival (PFS) was 13 months and overall survival 40 months. For responders, median duration of response was 13 months and median PFS 19 months. The most common adverse event (AE) of any grade was constipation (57.1%). The most common grade ≥ 3 AE was anemia (21.4%).
Conclusion
All in all, we hereby provide proof-of-concept that PI + IMiD may be an attractive backbone for fixed duration treatment. It should be noted that granting the same level of access to newer drugs globally is virtually impossible. Thus efforts to develop regimens using readily available drugs to yield similar or adequate treatment outcomes should not be disregarded. In this sense, we believe our study holds its place for its novelty and eloquently addresses achieving the daunting societal quest of health equity.

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Current Treatment Patterns and the Role of Upfront Autologous Stem Cell Transplantation in Patients with Peripheral T-Cell Lymphoma: A Korean Nationwide, Multicenter Prospective Registry Study (CISL 1404): Hyungwoo Cho, Dok Hyun Yoon, Dong-Yeop Shin, Youngil Koh, Sung-Soo Yoon, Seok Jin Kim, Young Rok Do, Gyeong-Won Lee, Jae-Yong Kwak, Yong Park, Min Kyoung Kim, Hye Jin Kang, Jun Ho Yi, Kwai Han Yoo, Won Sik Lee, Byeong Bae Park, Jae Cheol Jo, Hyeon-Seok Eom, Hyo Jung Kim, Seong Hyun Jeong, Young-Woong Won, Byeong Seok Sohn, Ji-Hyun Kwon, Cheolwon Suh, Won Seog Kim; Cancer Res Treat. 2023;55(2):684-692. Published online January 2, 2023; DOI: https://doi.org/10.4143/crt.2022.1434

Abstract PDF Supplementary Material PubReader ePub

Purpose
We conducted a nationwide, multicenter, prospective registry study for newly diagnosed patients with peripheral T-cell lymphoma (PTCL) to better define the clinical characteristics, treatment patterns, survival outcomes, and the role of upfront autologous stem cell transplantation (ASCT) in these patients.
Materials and Methods
Patients with PTCL receiving chemotherapy with curative intent were registered and prospectively monitored. All patients were pathologically diagnosed with PTCL.
Results
A total of 191 patients with PTCL were enrolled in this prospective registry study. PTCL, not otherwise specified (PTCL-NOS) was the most common pathologic subtype (n=80, 41.9%), followed by angioimmunoblastic T-cell lymphoma (AITL) (n=60, 31.4%). With a median follow-up duration of 3.9 years, the 3-year progression-free survival (PFS) and overall survival (OS) rates were 39.5% and 60.4%, respectively. The role of upfront ASCT was evaluated in patients who were considered transplant-eligible (n=59). ASCT was performed as an upfront consolidative treatment in 32 (54.2%) of these patients. There were no significant differences in PFS and OS between the ASCT and non-ASCT groups for all patients (n=59) and for patients with PTCL-NOS (n=26). However, in patients with AITL, the ASCT group was associated with significantly better PFS than the non-ASCT group, although there was no significant difference in OS.
Conclusion
The current study demonstrated that the survival outcomes with the current treatment options remain poor for patients with PTCL-NOS. Upfront ASCT may provide a survival benefit for patients with AITL, but not PTCL-NOS.

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Successful Treatment, with Chemotherapy and Intravenous Administration of Ascorbic Acid, of a Patient with Peripheral T-Cell Lymphoma, Not Otherwise Specified
Chiaki Tokoro, Atsushi Tashiro, Kenji Ina, Yoshiteru Tanaka, Hiroyuki Kobayakawa, Takashi Yoshida, Satoshi Kayukawa
Journal of Cancer Research Updates.2024; 13: 1. CrossRef
Role of upfront autologous transplant for peripheral T-cell lymphoma patients achieving a complete remission with first-line therapy: a systematic review and meta-analysis
L. Girard, Y. J. Koh, L. P. Koh, Y. L. Chee, H. L. Chan, J. Lee, S. de Mel, L. M. Poon, M. Samuel
Bone Marrow Transplantation.2024; 59(6): 838. CrossRef
Angioimmunoblastic T-cell lymphoma and correlated neoplasms with T-cell follicular helper phenotype: from molecular mechanisms to therapeutic advances
Luís Alberto de Pádua Covas Lage, Hebert Fabricio Culler, Cadiele Oliana Reichert, Sheila Aparecida Coelho da Siqueira, Juliana Pereira
Frontiers in Oncology.2023;[Epub] CrossRef
Advances in the pathogenesis and therapeutic strategies of angioimmunoblastic T-cell lymphoma
Qingyang Zhang, Le Yin, Qinqiao Lai, Yan Zhao, Hongling Peng
Clinical and Experimental Medicine.2023; 23(8): 4219. CrossRef

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Phase II Study of Dovitinib in Patients with Castration-Resistant Prostate Cancer (KCSG-GU11-05): Yoon Ji Choi, Hye Sook Kim, Se Hoon Park, Bong-Seog Kim, Kyoung Ha Kim, Hyo Jin Lee, Hong Suk Song, Dong-Yeop Shin, Ha Young Lee, Hoon-Gu Kim, Kyung Hee Lee, Jae Lyun Lee, Kyong Hwa Park; Cancer Res Treat. 2018;50(4):1252-1259. Published online January 2, 2018; DOI: https://doi.org/10.4143/crt.2017.438

Abstract PDF PubReader ePub

Purpose
Fibroblast growth factor (FGF) signals are important in carcinogenesis and progression of prostate cancer. Dovitinib is an oral, pan-class inhibitor of vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor, and fibroblast growth factor receptor (FGFR). We evaluated the efficacy and toxicity of dovitinib in men with metastatic castration resistant prostate cancer (mCRPC).
Materials and Methods
This study was a single-arm, phase II, open-label, multicenter trial of dovitinib 500 mg/day (5-days-on/2-days-off schedule). The primary endpointwas 16-week progression-free survival (PFS). Secondary endpoints were overall survival (OS), toxicity and prostate-specific antigen (PSA) response rate. Biomarker analyses for VEGFR2, FGF23, and FGFR2 using multiplex enzyme-linked immunosorbent assay was performed.
Results
Forty-four men were accrued from 11 hospitals. Eighty percent were post-docetaxel. Median PSA was 100 ng/dL, median age was 69, 82% had bone metastases, and 23% had liver metastases. Median cycles of dovitinibwas 2 (range, 0 to 33). Median PFSwas 3.67 months (95% confidence interval [CI], 1.36 to 5.98) and median OS was 13.70 months (95% CI, 0 to 27.41). Chemotherapy-naïve patients had longer PFS (17.90 months; 95% CI, 9.23 to 28.57) compared with docetaxel-treated patients (2.07 months; 95% CI, 1.73 to 2.41; p=0.001) and the patients with high serum VEGFR2 level over median level (7,800 pg/mL) showed longer PFS compared with others (6.03 months [95% CI, 4.26 to 7.80] vs. 1.97 months [95% CI, 1.79 to 2.15], p=0.023). Grade 3 related adverse events were seen in 40.9% of patients. Grade 1-2 nausea, diarrhea, fatigue, anorexia, and all grade thrombocytopenia are common.
Conclusion
Dovitinib showed modest antitumor activity with manageable toxicities in men with mCRPC. Especially, patients who were chemo-naïve benefitted from dovitinib.

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Invasion and metastasis in cancer: molecular insights and therapeutic targets
Yongxing Li, Fengshuo Liu, Qingjin Cai, Lijun Deng, Qin Ouyang, Xiang H.-F. Zhang, Ji Zheng
Signal Transduction and Targeted Therapy.2025;[Epub] CrossRef
Comprehensive Review on Recent Strategies for Management of Prostate Cancer: Therapeutic Targets and SAR
Manish Chaudhary, Shubham Kumar, Paranjeet Kaur, Sanjeev Kumar Sahu, Amit Mittal
Mini-Reviews in Medicinal Chemistry.2024; 24(7): 721. CrossRef
Impact of cell plasticity on prostate tumor heterogeneity and therapeutic response
Maddison Archer
American Journal of Clinical and Experimental Urology.2024; 12(6): 331. CrossRef
Role of Basic Fibroblast Growth Factor in Cancer: Biological Activity, Targeted Therapies, and Prognostic Value
Alessio Ardizzone, Valentina Bova, Giovanna Casili, Alberto Repici, Marika Lanza, Raffaella Giuffrida, Cristina Colarossi, Marzia Mare, Salvatore Cuzzocrea, Emanuela Esposito, Irene Paterniti
Cells.2023; 12(7): 1002. CrossRef
Case Report of a Glioma Patient with Homozygous Missense Amino Acid Substitution in KDR Gene
Kalyan Ram Uppaluri, Himavanth Reddy Kambalachenu, Hima Jyothi Challa, Saadvik Raghuram Y., Deepak Sharma, Ramya Gadicherla, Srinivas Ketavath, Kalyani Palasamudram, Sri Manjari K.
Indian Journal of Medical and Paediatric Oncology.2023; 44(03): 356. CrossRef
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Qing Liu, Jiyu Huang, Weiwei Yan, Zhen Liu, Shu Liu, Weiyi Fang
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Evaluation of the therapeutic potential of masitinib and expression of its specific targets c‐Kit, PDGFR‐α, PDGFR‐β, and Lyn in canine prostate cancer cell lines
Katharina Klose, Eva‐Maria Packeiser, José‐Luis Granados‐Soler, Marion Hewicker‐Trautwein, Hugo Murua Escobar, Ingo Nolte
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Elizabeth Liow, Nicholas Howard, Chol-Hee Jung, Bernard Pope, Bethany K. Campbell, Anne Nguyen, Michael Kerger, Jonathan B. Ruddle, Angelyn Anton, Benjamin Thomas, Kevin Chu, Philip Dundee, Justin S. Peters, Anthony J. Costello, Andrew S. Ryan, Christophe
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There are gremlins in prostate cancer
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Ankit Kumar Singh, Adarsh Kumar, Harshwardhan Singh, Pankaj Sonawane, Harshali Paliwal, Suresh Thareja, Prateek Pathak, Maria Grishina, Mariusz Jaremko, Abdul-Hamid Emwas, Jagat Pal Yadav, Amita Verma, Habibullah Khalilullah, Pradeep Kumar
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The FGF/FGFR system in the physiopathology of the prostate gland
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Signaling Pathways That Control Apoptosis in Prostate Cancer
Amaal Ali, George Kulik
Cancers.2021; 13(5): 937. CrossRef
A Review of the Pathophysiological Mechanisms Underlying Castration-resistant Prostate Cancer
Fionnuala Crowley, Michelle Sterpi, Conor Buckley, Lauren Margetich, Shivani Handa, Zach Dovey
Research and Reports in Urology.2021; Volume 13: 457. CrossRef
Neoadjuvant Treatment with Angiogenesis-Inhibitor Dovitinib Prior to Local Therapy in Hepatocellular Carcinoma: A Phase II Study
F.J. Sherida H. Woei-A-Jin, Nir I. Weijl, Mark C. Burgmans, Arantza Fariña Sarasqueta, J. Tom van Wezel, Martin N.J.M. Wasser, Minneke J. Coenraad, Jacobus Burggraaf, Susanne Osanto
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Reprogramming of Protein-Targeted Small-Molecule Medicines to RNA by Ribonuclease Recruitment
Peiyuan Zhang, Xiaohui Liu, Daniel Abegg, Toru Tanaka, Yuquan Tong, Raphael I. Benhamou, Jared Baisden, Gogce Crynen, Samantha M. Meyer, Michael D. Cameron, Arnab K. Chatterjee, Alexander Adibekian, Jessica L. Childs-Disney, Matthew D. Disney
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Bone microenvironment signaling of cancer stem cells as a therapeutic target in metastatic prostate cancer
Clara H. Lee, Ann M. Decker, Frank C. Cackowski, Russell S. Taichman
Cell Biology and Toxicology.2020; 36(2): 115. CrossRef
Brivanib, a multitargeted small‐molecule tyrosine kinase inhibitor, suppresses laser‐induced CNV in a mouse model of neovascular AMD
Lele Li, Manhui Zhu, Wenli Wu, Bai Qin, Jiayi Gu, Yuanyuan Tu, Jianing Chen, Dong Liu, Yunwei Shi, Xiaojuan Liu, Aimin Sang, Dongmei Ding
Journal of Cellular Physiology.2020; 235(2): 1259. CrossRef
In Vitro Effect of Dovitinib (TKI258), a Multi-Target Angiokinase Inhibitor on Aggressive Meningioma Cells
Arabinda Das, Jaime L. Martinez Santos, Mohammed Alshareef, Guilherme Bastos Ferreira Porto, Libby Kosnik Infinger, William A. Vandergrift, Scott M. Lindhorst, Abhay K. Varma, Sunil J. Patel, David Cachia
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Potential Role of Targeting KDR and Proteasome Inhibitors in the Therapy of Esophageal Squamous Cell Carcinoma
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Technology in Cancer Research & Treatment.2020;[Epub] CrossRef
Novel Therapeutic Strategies for CDK4/6 Inhibitors in Metastatic Castrate-Resistant Prostate Cancer

Adam M. Kase, John A. Copland, Winston Tan
OncoTargets and Therapy.2020; Volume 13: 10499. CrossRef
Therapeutic implications of fibroblast growth factor receptor inhibitors in a combination regimen for solid tumors (Review)
Hong Luo, Tao Zhang, Peng Cheng, Dong Li, Oleksandr Ogorodniitchouk, Chaimaa Lahmamssi, Ge Wang, Meiling Lan
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Dovitinib Triggers Apoptosis and Autophagic Cell Death by Targeting SHP-1/p-STAT3 Signaling in Human Breast Cancers
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Tumour-stroma ratio and 5-year mortality in gastric adenocarcinoma: a systematic review and meta-analysis
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A Novel FGFR3 Splice Variant Preferentially Expressed in African American Prostate Cancer Drives Aggressive Phenotypes and Docetaxel Resistance
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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

Abstract PDF PubReader ePub

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.

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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
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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
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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
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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
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Case Report

A Case of Erdheim-Chester Disease with Asymptomatic Renal Involvement: Hyun Jung Lee, Kyoung Yul Lee, Dong-Yeop Shin, Yun Gyoo Lee, Se Youn Choi, Kyung Chul Moon, Il-Kyu Han, Tae Min Kim; Cancer Res Treat. 2012;44(2):146-150. Published online June 30, 2012; DOI: https://doi.org/10.4143/crt.2012.44.2.146

Abstract PDF PubReader ePub

Erdheim-Chester disease is a rare non-Langerhans-cell histiocytosis involving bones and multiple organs. Its clinical course can vary, from an asymptomatic state to a fatal disease, with renal involvement being a common cause of death. A 41-year-old man presented with a 10-month history of bilateral lower limb pain. Left perirenal soft-tissue infiltration had been found incidentally two years earlier. No progression of the lesion or deterioration of renal function was observed for a period of two years. At admission, plain radiography and magnetic resonance imaging of the patient's lower limbs showed patchy osteosclerosis. Biopsy of the tibia revealed histiocytic infiltration, which was found to be positive for CD68 and negative for CD1a. This report describes an unusual case of Erdheim-Chester disease involving a stationary course of disease with no specific treatment for a long period of time.

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Erdheim–Chester disease. Literature review and clinical case
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