Uson Junior Pedro Luiz Serrano, Bearss Jeremiah, Babiker Hani M, Borad Mitesh J
Division of Hematology & Oncology, Department of Medicine, Mayo Clinic, Scottsdale, AZ, USA.
Center for Personalized Medicine, Hospital Israelita Albert Einstein, São Paulo, Brazil.
Expert Opin Investig Drugs. 2023 Jan;32(1):69-75. doi: 10.1080/13543784.2023.2173064. Epub 2023 Jan 30.
The treatment landscape of biliary cancers is rapidly changing. Inhibitors against the actionable targets FGFR and IDH1 are now being included in the treatment guidelines of multiple countries for patients with advanced cholangiocarcinoma. However, there remains an unmet need in identifying the mechanisms of resistance and treatment strategies involving possible tumor sequencing.
In this review article, we address clinical trials evaluating FGFR, IDH, BRAF and HER2 inhibitors in advanced cholangiocarcinoma. We also review the mechanisms of resistance described thus far and approaches to overcome them. Articles selected for this review were based on reported studies indexed in PubMed (2010-2022).
Precision medicine in biliary cancers has already been incorporated into the treatment landscape of the disease in many countries. Fusions of FGFR2 and mutations in IDH1 are the first drivers with targetable treatments approved in these cancers. HER2 and BRAF would be the next drivers with possible tumor-agnostic or cholangiocarcinoma-specific approvals. The advent of ctDNA could improve the accessibility of sequencing and recruitment in these clinical trials. However, limitations of detecting fusions should be considered and addressed in these platforms.
胆管癌的治疗格局正在迅速变化。针对可操作靶点FGFR和IDH1的抑制剂现已被纳入多个国家晚期胆管癌患者的治疗指南。然而，在确定耐药机制和涉及可能的肿瘤测序的治疗策略方面，仍存在未满足的需求。
在这篇综述文章中，我们阐述了评估FGFR、IDH、BRAF和HER2抑制剂用于晚期胆管癌的临床试验。我们还回顾了迄今为止所描述的耐药机制以及克服这些机制的方法。入选本综述的文章基于PubMed（2010 - 2022年）收录的已报道研究。
胆管癌的精准医学已在许多国家被纳入该疾病的治疗格局。FGFR2融合和IDH1突变是这些癌症中首批有可靶向治疗获批的驱动因素。HER2和BRAF将是接下来可能获得肿瘤非特异性或胆管癌特异性批准的驱动因素。循环肿瘤DNA（ctDNA）的出现可提高这些临床试验中测序和招募的可及性。然而，在这些平台中应考虑并解决检测融合的局限性。
