Vogel Arndt, Segatto Oreste, Stenzinger Albrecht, Saborowski Anna
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; email:
Center for Personalized Medicine (ZPM), Hannover Medical School, Hannover, Germany.
Annu Rev Med. 2023 Jan 27;74:293-306. doi: 10.1146/annurev-med-042921-024707. Epub 2022 Sep 28.
Biliary tract cancer (BTC) is the second most common primary liver cancer after hepatocellular carcinoma and accounts for 2% of cancer-related deaths. BTCs are classified according to their anatomical origin into intrahepatic (iCCA), perihilar, or distal cholangiocarcinoma, as well as gall bladder carcinoma. While the mutational profiles in these anatomical BTC subtypes overlap to a large extent, iCCA is notable for the high frequency of IDH1/2 mutations (10-22%) and the nearly exclusive occurrence of FGFR2 fusions in 10-15% of patients. In recent years, FGFR2 fusions have become one of the most promising targets for precision oncology targeting BTC, with FGFR inhibitors already approved in Europe and the United States for patients with advanced, pretreated iCCA. While the therapeutic potential of nonfusion alterations is still under debate, it is expected that the field of FGFR2-directed therapies will be subject to rapid further evolution and optimization. The scope of this review is to provide an overview of oncogenic FGFR signaling in iCCA cells and highlight the pathophysiology, diagnostic testing strategies, and therapeutic promises and challenges associated with FGFR2-altered iCCA.
胆管癌（BTC）是继肝细胞癌之后第二常见的原发性肝癌，占癌症相关死亡人数的2%。BTC根据其解剖学起源可分为肝内胆管癌（iCCA）、肝门周围或远端胆管癌以及胆囊癌。虽然这些解剖学上的BTC亚型的突变谱在很大程度上重叠，但iCCA的显著特点是IDH1/2突变频率高（10%-22%），且10%-15%的患者中几乎仅出现FGFR2融合。近年来，FGFR2融合已成为精准肿瘤学针对BTC最有前景的靶点之一，FGFR抑制剂已在欧洲和美国获批用于治疗晚期、经预处理的iCCA患者。虽然非融合改变的治疗潜力仍在争论中，但预计FGFR2导向治疗领域将迅速进一步发展和优化。本综述的范围是概述iCCA细胞中致癌性FGFR信号传导，并强调与FGFR2改变的iCCA相关的病理生理学、诊断测试策略以及治疗前景和挑战。
