Cancer Research and Treatment

Original Articles

Endocrine cancer

Combination of Dabrafenib and Trametinib in Patients with Metastatic BRAF^V600E-Mutated Thyroid Cancer: Youngkyung Jeon, Sehhoon Park, Se-Hoon Lee, Tae Hyuk Kim, Sun Wook Kim, Myung-Ju Ahn, Hyun Ae Jung, Jae Hoon Chung; Cancer Res Treat. 2024;56(4):1270-1276. Published online March 6, 2024; DOI: https://doi.org/10.4143/crt.2023.1278

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Purpose
BRAF mutations are detected in 30%-80% of papillary thyroid cancer (PTC) cases. DaBRAFenib and trametinib showed promising antitumor activity in patients with BRAF^V600E-mutated metastatic melanoma and non–small cell lung cancer. This study aimed to evaluate the efficacy and safety of daBRAFenib and trametinib in patients with metastatic BRAF^V600E-mutated thyroid cancer.
Materials and Methods
This was a retrospective study to evaluate the efficacy of daBRAFenib and trametinib in patients with metastatic BRAF^V600E-mutated PTC. The patients received daBRAFenib 150 mg twice daily and trametinib 2 mg once daily at the Samsung Medical Center. This study evaluated the progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) overall survival (OS), and safety of daBRAFenib and trametinib.
Results
Between December 2019 and January 2022, 27 PTC patients including eight patients with poorly differentiated or anaplastic transformation, received daBRAFenib and trametinib. The median age was 73.0 years, and the median follow-up period was 19.8 months. The majority (81.5%) had undergone thyroidectomy, while 8 patients had received prior systemic treatments. ORR was 73.1%, with 19 partial responses, and DCR was 92.3%. Median PFS was 21.7 months, and median OS was 21.7 months. Treatment-related adverse events included generalized weakness (29.6%), fever (25.9%), and gastrointestinal problems (22.2%). Dose reduction due to adverse events was required in 81.5% of the patients.
Conclusion
DaBRAFenib and trametinib demonstrated a high ORR with promising PFS; however, most patients with BRAF^V600E-mutated metastatic PTC required a dose reduction.

Citations

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Intracranial antitumor efficacy of combination treatment with encorafenib plus binimetinib in BRAF V600E-mutated anaplastic thyroid carcinoma
Ryutaro Onaga, Tomohiro Enokida, Toshifumi Tomioka, Shingo Sakashita, Masanobu Sato, Nobukazu Tanaka, Yuta Hoshi, Takuma Kishida, Ryo Kuboki, Takao Fujisawa, Susumu Okano, Kazuto Matsuura, Makoto Tahara
Auris Nasus Larynx.2026; 53(1): 7. CrossRef
BRAF and MEK inhibition beyond dabrafenib–trametinib in advanced thyroid cancer: a real-world case series
Tzahi Yamin, Oded Cohen, Eyal Robenshtok, Elena Izkhakov, Mor Miodovnik, Orit Gutfeld, Yasmin Leshem, Roman Meirovitz, Anton Warshavsky, Nidal Muhanna, Inbar Finkel
Frontiers in Endocrinology.2026;[Epub] CrossRef
Declined RTN3 stabilizes DHCR7 to induce cholesterol-dependent tumor progression and MEK inhibitors insensitivity in thyroid cancer
Anwen Ren, Nan Feng, Tinglin Yang, Zimei Tang, Huan Liu, Yi Li, Qingyi Hu, Zihan Xi, Jiaqing Zhu, Jun Zhou, Jie Ming, Nan Liu, Tao Huang, Ming Xu
Cell Death & Disease.2026;[Epub] CrossRef
A comprehensive review of RAF kinase: advances in inhibition strategies for drug development
Dilay Kahvecioglu
Journal of Molecular Structure.2025; 1337: 142206. CrossRef
Development of a coagulation‑related gene model for prognostication, immune response and treatment prediction in lung adenocarcinoma
Jia Li, Xuedi Gao, Lin Lv, Yubin Huang, Houlu Zhang, Xiaoming Sun, Liangming Zhu
Oncology Letters.2025; 29(6): 1. CrossRef
Systemic Therapeutic Options in Radioiodine-Refractory Differentiated Thyroid Cancer: Current Indications and Optimal Timing
Tamara Díaz Vico, Brezo Martínez-Amores Martínez, Luka Mihic Góngora, Paula Jiménez-Fonseca, Paloma Peinado Martín, Irene Grao Torrente, Alejandro García Muñoz-Nájar, Manuel Durán-Poveda
Cancers.2025; 17(11): 1800. CrossRef
Thyroid Cancer: Epidemiology, Classification, Risk Factors, Diagnostic and Prognostic Markers, and Current Treatment Strategies
Alicja Forma, Karolina Kłodnicka, Weronika Pająk, Jolanta Flieger, Barbara Teresińska, Jacek Januszewski, Jacek Baj
International Journal of Molecular Sciences.2025; 26(11): 5173. CrossRef
A single-center retrospective study of dabrafenib plus trametinib combination therapy in patients with BRAF V600E-positive thyroid cancer
Taiju Ando, Yuko Oya, Yumi Tomiie, Kimio Ogawa, Tomoki Kuki, Yosuke Tanabe, Hisayuki Kato, Kazuyoshi Imaizumi, Yatsuka Hibi, Kenji Kawada
International Journal of Clinical Oncology.2025; 30(11): 2257. CrossRef
Tumor response and thyroglobulin change in differentiated thyroid carcinoma treated with dabrafenib plus trametinib
Haruhiko Yamazaki, Nobuyasu Suganuma, Mei Kadoya, Katsuhiko Masudo, Soji Toda, Aya Saito
Cancer Chemotherapy and Pharmacology.2025;[Epub] CrossRef
Progress in Drug-targeted Therapy for Papillary Thyroid Carcinoma
Bin Wang, Limin Xu, Menglong Rui
Current Oncology Reports.2025; 27(11): 1331. CrossRef
Korean Thyroid Association Guidelines on the Management of Differentiated Thyroid Cancers; Part III. Management of Advanced Differentiated Thyroid Cancers - Chapter 4. Systemic Therapy for Progressive Radioiodine-Refractory Differentiated Thyroid Cancer 2
Dong Yeob Shin, Ho-Cheol Kang, Sun Wook Kim, Dong Gyu Na, Young Joo Park, Young Shin Song, Eun Kyung Lee, Dong-Jun Lim, Yun Jae Chung, Won Gu Kim
International Journal of Thyroidology.2024; 17(1): 168. CrossRef
Antineoplastic Effect of ALK Inhibitor Crizotinib in Primary Human Anaplastic Thyroid Cancer Cells with STRN–ALK Fusion In Vitro
Silvia Martina Ferrari, Francesca Ragusa, Giusy Elia, Valeria Mazzi, Eugenia Balestri, Chiara Botrini, Licia Rugani, Armando Patrizio, Simona Piaggi, Concettina La Motta, Salvatore Ulisse, Camilla Virili, Alessandro Antonelli, Poupak Fallahi
International Journal of Molecular Sciences.2024; 25(12): 6734. CrossRef
The Long Journey towards Personalized Targeted Therapy in Poorly Differentiated Thyroid Carcinoma (PDTC): A Case Report and Systematic Review
Odysseas Violetis, Panagiota Konstantakou, Ariadni Spyroglou, Antonios Xydakis, Panagiotis B. Kekis, Sofia Tseleni, Denise Kolomodi, Manousos Konstadoulakis, George Mastorakos, Maria Theochari, Javier Aller, Krystallenia I. Alexandraki
Journal of Personalized Medicine.2024; 14(6): 654. CrossRef
Treatment of Unresectable BRAF V600E, TERT-Mutated Differentiated Papillary Thyroid Cancer With Dabrafenib and Trametinib
Neha Bapat, Tatiana Ferraro, Layal Esper, Arjun S Joshi, Faysal Haroun, Chelsey K Baldwin
JCEM Case Reports.2024;[Epub] CrossRef
Trametinib

Reactions Weekly.2024; 2035(1): 467. CrossRef

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Genitourinary cancer

Neoadjuvant Cisplatin-Based Chemotherapy Followed by Selective Bladder Preservation Chemoradiotherapy in Muscle-Invasive Urothelial Carcinoma of the Bladder: Post Hoc Analysis of Two Prospective Studies: Sung Wook Cho, Sung Hee Lim, Ghee Young Kwon, Chan Kyo Kim, Won Park, Hongryull Pyo, Jae Hoon Chung, Wan Song, Hyun Hwan Sung, Byong Chang Jeong, Se Hoon Park; Cancer Res Treat. 2024;56(3):893-897. Published online February 15, 2024; DOI: https://doi.org/10.4143/crt.2024.015

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Purpose
Bladder preservation chemoradiotherapy (CRT) in patients with a clinical complete response (cCR) following cisplatin-based neoadjuvant chemotherapy (NAC) is a promising treatment strategy for muscle-invasive bladder urothelial carcinoma (MIBC). A combined analysis of raw data from two prospective phase II studies was performed to better evaluate the feasibility of selective bladder preservation CRT.
Materials and Methods
The analysis was based on primary efficacy data from two independent studies, including 76 MIBC patients receiving NAC followed by bladder preservation CRT. The efficacy data included metastasis-free survival (MFS) and disease-free survival (DFS). For the present analysis, starting point of survival was defined as the date of commencing CRT.
Results
Among 76 patients, 66 had a cCR following NAC. Sixty-four patients received gemcitabine and cisplatin (GC) combination chemotherapy in neoadjuvant setting, and 12 received nivolumab plus GC. Bladder preservation CRT following NAC was generally well-tolerated, with low urinary tract symptoms being the most common late complication. With a median follow-up of 64 months, recurrence was recorded in 43 patients (57%): intravesical only (n=20), metastatic only (n=16), and both (n=7). In 27 patients with intravesical recurrence, transurethral resection, and Bacillus Calmette-Guerin treatment was given to 17 patients. Salvage cystectomy was performed in 10 patients. Median DFS was 46.3 (95% confidence interval [CI], 25.1 to 67.5) months, and the median MFS was not reached. Neither DFS nor MFS appeared to be affected by any of the baseline characteristics. However, DFS was significantly longer in patients with a cCR than in those without (hazard ratio, 0.465; 95% CI, 0.222 to 0.976).
Conclusion
The strategy of NAC followed by selective bladder preservation CRT based on the cCR is feasible in the treatment of MIBC. A standardized definition of cCR is needed to better assess disease status post-NAC.

Citations

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Neoadjuvant Chemotherapy Prior to Trimodality Therapy for Muscle-invasive Bladder Cancer: A Systematic Review and Meta-analysis
Keiichiro Miyajima, Akihiro Matsukawa, Takafumi Yanagisawa, Marcin Miszczyk, Navid Roessler, Shota Inoue, Abdulrahman S. Alqahtani, Ahmed R. Alfarhan, Fumihiko Urabe, Keiichiro Mori, Pierre I. Karakiewicz, Takahiro Kimura, Shahrokh F. Shariat
European Urology Open Science.2026; 83: 54. CrossRef
Comparative Outcomes of Surgery and Chemoradiotherapy After Neoadjuvant Chemotherapy in Stage II–III Bladder Cancer
Doğan Bayram, Öznur Bal, Alper Türkel, Serhat Sekmek, Emre Hafızoğlu, Berkan Karabuga, Mutlu Doğan, Efnan Algın, Doğan Uncu
The European Research Journal.2026; 12(2): 160. CrossRef
Bladder Preservation with Concurrent Chemoradiotherapy Following Complete Response to Induction Systemic Therapy in Patients with Muscle-Invasive Bladder Cancer: A Review of the Existing Literature
Georgios Nikiforos Ntoumas, Andromachi Kougioumtzopoulou, Dimitra Desse, Charalambos Fragkoulis, Georgios Papadopoulos, Efthymios Kostouros, Dimitra Michaletou, Vassileios Kouloulias, Anna Zygogianni, Ioannis Georgakopoulos
Cancers.2026; 18(6): 961. CrossRef
Recent Advances and Future Directions in Bladder Preservation Therapy for Muscle‐Invasive Bladder Cancer
Tomokazu Kimura, Satoshi Inoue, Tomoyasu Sano, Kenji Zennami, Shusuke Akamatsu
International Journal of Urology.2025; 32(10): 1334. CrossRef
Prognostic Factors of Trimodal Therapy for Muscle-invasive Bladder Cancer: A Systematic Review and Meta-analysis
Keiichiro Miyajima, Akihiro Matsukawa, Takafumi Yanagisawa, Marcin Miszczyk, Navid Roessler, Shota Inoue, Shingo Nishimura, Abdulrahman S. Alqahtani, Ahmed R. Alfarhan, Fumihiko Urabe, Keiichiro Mori, Pierre I. Karakiewicz, Leonardo Oliveira Reis, Takahir
European Urology Focus.2025;[Epub] CrossRef
Assessing clinical complete response after neoadjuvant systemic therapy in muscle-invasive bladder cancer: a systematic review
Navid Roessler, Marcin Miszczyk, Paolo Gontero, Keiichiro Miyajima, Shota Inoue, Ahmed R. Alfarhan, Abdulrahman S. Alqahtani, Markus von Deimling, Malte W. Vetterlein, Jeremy Yuen-Chun Teoh, David D’Andrea, Margit Fisch, Shahrokh F. Shariat
World Journal of Urology.2025;[Epub] CrossRef
News and prospects on radiotherapy for bladder cancer: Is trimodal therapy becoming the gold standard?
Olivier Riou, Christophe Hennequin, Jonathan Khalifa, Paul Sargos
Cancer/Radiothérapie.2024; 28(6-7): 623. CrossRef

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Single Early Intravesical Instillation of Epirubicin for Preventing Bladder Recurrence after Nephroureterectomy in Upper Urinary Tract Urothelial Carcinoma: Jong Hoon Lee, Chung Un Lee, Jae Hoon Chung, Wan Song, Minyong Kang, Hwang Gyun Jeon, Byong Chang Jeong, Seong Il Seo, Seong Soo Jeon, Hyun Hwan Sung; Cancer Res Treat. 2024;56(3):877-884. Published online January 17, 2024; DOI: https://doi.org/10.4143/crt.2023.1219

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Purpose
We aimed to assess the effectiveness of early single intravesical administration of epirubicin in preventing intravesical recurrence after radical nephroureterectomy for upper tract urothelial carcinoma.
Materials and Methods
Patients with upper tract urothelial carcinoma who underwent radical nephroureterectomy between November 2018 and May 2022 were retrospectively reviewed. Intravesical epirubicin was administered within 48 hours if no evidence of leakage was observed. Epirubicin (50 mg) in 50 mL normal saline solution was introduced into the bladder via a catheter and maintained for 60 minutes. The severity of adverse events was graded using the Clavien-Dindo classification. We compared intravesical recurrence rate between the two groups. Multivariate analyses were performed to identify the independent predictors of bladder recurrence following radical nephroureterectomy.
Results
Epirubicin (n=55) and control (n=116) groups were included in the analysis. No grade 1 or higher bladder symptoms have been reported. A statistically significant difference in the intravesical recurrence rate was observed between the two groups (11.8% at 1 year in the epirubicin group vs. 28.4% at 1 year in the control group; log-rank p=0.039). In multivariate analysis, epirubicin instillation (hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.20 to 0.93; p=0.033) and adjuvant chemotherapy (HR, 0.29; 95% CI, 0.13 to 0.65; p=0.003) were independently predictive of a reduced incidence of bladder recurrence.
Conclusion
This retrospective review revealed that a single immediate intravesical instillation of epirubicin is safe and can reduce the incidence of intravesical recurrence after radical nephroureterectomy. However, further prospective trials are required to confirm these findings.

Citations

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Immediate Vs. Delayed single post-operative intravesical instillation of chemotherapy in reducing bladder recurrence rate in upper tract urothelial carcinoma patients after radical nephroureterectomy
Yiwen Liu, Yun Song, Nienie Qi, Chong Han, Meng Lu, Meng Zhang, Rumin Wen, Xiaoxiao Jiang, Hailong Li
World Journal of Urology.2026;[Epub] CrossRef
The role of intravesical chemotherapy following nephroureterectomy in upper tract urothelial carcinoma: A systematic review and meta-analysis
Stefano Moretto, Andrea Piccolini, Andrea Gallioli, Roberto Contieri, Nicolomaria Buffi, Giovanni Lughezzani, Alberto Breda, Michael Baboudjian, Bas WG van Rhijn, Morgan Roupret, Alessandro Uleri, Benjamin Pradere
Urologic Oncology: Seminars and Original Investigations.2025; 43(3): 191.e1. CrossRef
Prognostic Value of the De Ritis Ratio in Predicting Survival After Bladder Recurrence Following Nephroureterectomy for Upper Urinary Tract Tumors
Enis Mert Yorulmaz, Kursad Donmez, Serkan Ozcan, Osman Kose, Sacit Nuri Gorgel, Enes Candemir, Yigit Akin
Diagnostics.2025; 15(15): 1840. CrossRef
Scientific advances in drug development and clinical trials for urothelial carcinoma: Highlights from the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium
Ruicheng Wu, Dengxiong Li, Dechao Feng
Asian Journal of Urology.2025;[Epub] CrossRef

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Adjuvant Chemotherapy for Upper Tract Urothelial Carcinoma: A Real-World, Retrospective Study: Junho Lee, Sung Hee Lim, Jae Hoon Chung, Wan Song, Hyun Hwan Sung, Byong Chang Jeong, Se Hoon Park; Cancer Res Treat. 2024;56(3):871-876. Published online January 16, 2024; DOI: https://doi.org/10.4143/crt.2023.1226

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Purpose
The aim of this retrospective study was to evaluate the efficacy of adjuvant cisplatin-based chemotherapy in patients with locally advanced upper tract urothelial carcinoma (UTUC), administered following radical nephroureterectomy.
Materials and Methods
Patients with UTUC, arising from renal pelvis or ureter, staged pT3/T4 or N+ were treated with adjuvant chemotherapy following surgery. The chemotherapy consisted of gemcitabine 1,000 mg/m² on days 1 and 8, cisplatin 70 mg/m² on day 1. Treatment was repeated every 3 weeks for up to 4 cycles. Endpoints included disease-free survival (DFS), metastasis-free survival (MFS), and safety.
Results
Among 89 eligible patients, 85 (95.5%) completed at least 3 cycles of adjuvant chemotherapy. Chemotherapy was well tolerated, the main toxicities being mild-to-moderate gastrointestinal toxic effects and pruritus. With a median follow-up of 37 months, median DFS was 30 months (95% confidence interval, 22 to 39), and the median MFS was not reached. The 3-year DFS and MFS were 44% and 56%, respectively. Multivariate analyses revealed that the main factor associated with DFS and MFS was the lymph node involvement, whereas age, T category, grade, or the primary site of UTUC were not significantly associated with DFS or MFS.
Conclusion
Adjuvant cisplatin-based chemotherapy after radical surgery of pT3/T4 or N+ UTUC was feasible and may demonstrate benefits in DFS and MFS. Whether novel agents added to the chemotherapy regimen, as a concurrent combination or maintenance, impacts on survival or reduces the development of metastases remains to be studied.

Citations

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Perioperative and oncological outcomes of single position retroperitoneoscopic radical nephroureterectomy for upper urinary tract urothelial carcinoma
Jiaqiang Chen, Luxin Zhang, Zhihong Dai, Cheng Chang, Heyao Tong, Hepeng Cui, Zhuwei Song, Bo Fan, Zhiyu Liu, Liang Wang
Scientific Reports.2025;[Epub] CrossRef
Scientific advances in drug development and clinical trials for urothelial carcinoma: Highlights from the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium
Ruicheng Wu, Dengxiong Li, Dechao Feng
Asian Journal of Urology.2025;[Epub] CrossRef
Cisplatin/gemcitabine

Reactions Weekly.2024; 2027(1): 127. CrossRef

6,548 View
154 Download
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