Cancer Research and Treatment

Original Articles

Clinico-Pathologic Features of Adult Erdheim–Chester Disease in South Korea: A Multicenter Retrospective Study (KCSG LY22-15): Ji Yun Lee, Heounjeong Go, Myung-won Lee, Ji Hyun Lee, Sang Eun Yoon, Jee Hyun Kong, Sojung Lim, Yoon Kyung Jeon, Tae Min Kim; Received April 14, 2026 Accepted June 22, 2026 Published online June 29, 2026; DOI: https://doi.org/10.4143/crt.2026.0404 [Accepted]

Abstract PDF: Purpose
Erdheim–Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterized by heterogeneous multisystem manifestations and frequent MAPK–ERK pathway alterations. Data on the clinico-pathologic features and real-world outcomes of adult ECD in South Korea are limited.
Materials and Methods
We conducted a retrospective multicenter cohort study of adult patients (≥18 years) with ECD at seven Korean Cancer Study Group (KCSG)-affiliated institutions between October 2008 and June 2024. Clinical and pathologic features, BRAF V600E mutation status, treatment patterns, and overall survival (OS) were analyzed using the Kaplan–Meier method.
Results
Twenty-two patients were included (median age 57 years [IQR 45–64]; 50% male). Organ involvement was heterogeneous: bone (54.5%), retroperitoneal/renal (31.8%), central nervous system (27.3%), cardiovascular (27.3%), hypothalamic-pituitary axis (27.3%), pulmonary (18.2%), and skin (13.6%); multisystem disease (≥2 organs) was present in 40.9%. BRAF V600E was positive in 11 of 19 tested patients (57.9%). Systemic treatment was initiated in 18 patients (81.8%); interferon-α-based regimens were the most common first-line approach (50.0%). Among 16 evaluable patients, the disease control rate (CR/PR/SD) was 87.5%. With a median follow-up of 4.6 years (IQR 1.3–6.5), 2- and 5-year OS rates were 90.0% and 74.3%, respectively.
Conclusion
Korean adult patients with ECD demonstrate heterogeneous organ involvement and frequent BRAF V600E positivity. Real-world treatment remains dominated by interferon-α-based approaches, underscoring the need for standardized molecular testing and improved access to targeted therapy.

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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

Abstract PDF Supplementary Material PubReader ePub

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

Citations to this article as recorded by

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
Gene alterations in differentiated thyroid cancer and iodine therapy: Mechanisms and clinical implications
Yujun Wu, Li Zhang, Jinbo Gui, Jingwen Wang, Xiaoyan Long, Xiaoli Lan, Yansong Lin, Wei Cao
Journal of Nuclear Medicine and Molecular Imaging.2026;[Epub] CrossRef
Management of recurrent papillary thyroid carcinoma: diagnosis, surveillance, and treatment strategies
Jin-Choon Lee
Korean Intraoperative Neuromonitoring Society.2026; 6(1): 70. CrossRef
Efficacy and safety of dabrafenib plus trametinib in adults with differentiated thyroid cancer: a randomised, double-blind, placebo-controlled, phase 3 trial
Ming Gao, Young Joo Park, Chia-Chi Lin, Monika K Krzyzanowska, Zhiyong Li, Hui-Jen Tsai, Feng Shi, Jianwu Qin, Swee Hsia Choong, Yansong Lin, Yuan Zhang, Jin H Kang, Ana O Hoff, Monique Tan, Michael Roughton, Michaela Paul, Lori J Wirth
The Lancet Oncology.2026; 27(8): 994. CrossRef
How to manage radioiodine-refractory thyroid cancer in the era of precision medicine
Olga Karapanou, Grigoris Effraimidis, Marina Michalaki, Katerina Saltiki
Drugs in Context.2026; : 1. CrossRef
Efficacy and safety of dabrafenib plus trametinib in BRAFV600E-mutated advanced thyroid carcinoma: Real world experience in 37 patients
Haruhiko Yamazaki, Nobuyasu Suganuma, Mei Kadoya, Katsuhiko Masudo, Ai Matsui, Aya Saito
Endocrine Journal.2026; 73(9): 1045. 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

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Pediatric cancer

Effectiveness and Safety of Dabrafenib in the Treatment of 20 Chinese Children with BRAF^V600E-Mutated Langerhans Cell Histiocytosis: Ying Yang, Dong Wang, Lei Cui, Hong-Hao Ma, Li Zhang, Hong-Yun Lian, Qing Zhang, Xiao-Xi Zhao, Li-Ping Zhang, Yun-Ze Zhao, Na Li, Tian-You Wang, Zhi-Gang Li, Rui Zhang; Cancer Res Treat. 2021;53(1):261-269. Published online September 15, 2020; DOI: https://doi.org/10.4143/crt.2020.769

Abstract PDF Supplementary Material PubReader ePub

Purpose
We sought to investigate the effectiveness and safety of dabrafenib in children with BRAF^V600E-mutated Langerhans cell histiocytosis (LCH).
Materials and Methods
A retrospective analysis was performed on 20 children with BRAF^V600E-mutated LCH who were treated with dabrafenib.
Results
The median age at which the patients started taking dabrafenib was 2.3 years old (range, 0.6 to 6.5 years). The ratio of boys to girls was 2.3:1. The median follow-up time was 30.8 months (range, 18.9 to 43.6 months). There were 14 patients (70%) in the risk organ (RO)⁺ group and six patients (30%) in the RO^– group. All patients were initially treated with traditional chemotherapy and then shifted to targeted therapy due to poor control of LCH or intolerance to chemotherapy. The overall objective response rate and the overall disease control rate were 65% and 75%, respectively. During treatment, circulating levels of cell-free BRAF^V600E (cfBRAF^V600E) became negative in 60% of the patients within a median period of 3.0 months (range, 1.0 to 9.0 months). Grade 2 or 3 adverse effects occurred in five patients.
Conclusion
Some children with BRAF^V600E-mutated LCH may benefit from monotherapy with dabrafenib, especially high-risk patients with concomitant hemophagocytic lymphohistiocytosis and intolerance to chemotherapy. The safety of dabrafenib is notable. A prospective study with a larger sample size is required to determine the optimal dosage and treatment duration.

Citations

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Upregulation of MicroRNA-1246 Is Associated with BRAF Inhibitor Resistance in Melanoma Cells with Mutant BRAF: Jae-Hyeon Kim, Jun-Ho Ahn, Michael Lee; Cancer Res Treat. 2017;49(4):947-959. Published online January 3, 2017; DOI: https://doi.org/10.4143/crt.2016.280

Abstract PDF Supplementary Material PubReader ePub

Purpose
Intrinsic and acquired resistance limit the therapeutic benefits of inhibitors of oncogenic BRAF in melanoma. To identify microRNAs (miRNAs) associated with resistance to a BRAF inhibitor, we compared miRNA expression levels in three cell lines with different BRAF inhibitor sensitivity.
Materials and Methods
miRNA microarray analysis was conducted to compare miRNA expression levels. Real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was performed to confirm the expression of differentially expressed miRNAs. The cellular effects of miR-1246 were further examined by MTT assay, immunoblotting analysis, cell cycle analysis, flow cytometric assay of apoptosis, and autophagy assay.
Results
The miRNA microarray analysis and qRT-PCR identified five miRNAs (miR-3617, miR-92a-1, miR-1246, miR-193b-3p, and miR-17-3p) with expression that was consistently altered in two BRAF inhibitor-resistant cell lines. Among the five miRNAs, a miR-1246 mimic significantly reduced the antiproliferative effects of the BRAF inhibitor PLX4720 in BRAF inhibitor–resistant A375P (A375P/Mdr) cells, suggesting that miR-1246 upregulation confers acquired resistance to BRAF inhibition. In particular, apoptosis was identified as a major type of cell death in miR-1246–transfected cells; however, necrosis predominated in mimic-control-transfected cells, indicating that the resistance to PLX4720 in miR-1246 mimic-transfected cells is predominantly due to a reduction in necrosis. Furthermore, we found that miR-1246 promoted G2/M arrest through autophagy as a way to escape cell death by necrosis and apoptosis in response to PLX4720. The promotion of BRAF inhibitor resistance by miR-1246 was associated with lowered levels of p-ERK.
Conclusion
These results suggest that miR-1246 may be a potential therapeutic target in melanoma with acquired resistance to BRAF inhibitors.

Citations

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Biomedicine & Pharmacotherapy.2017; 92: 972. CrossRef

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