Department of Medical Oncology (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.
Zhejiang Provincial Clinical Research Center for Cancer, Hangzhou, Zhejiang Province, China.
J Dig Dis. 2023 Feb;24(2):85-97. doi: 10.1111/1751-2980.13168. Epub 2023 May 5.
Biliary tract cancers (BTCs) are aggressive tumors of the biliary system, which are often diagnosed at the advanced stage with a dismal prognosis. Among BTC patients, germline or somatic breast cancer-related gene 1/2 (BRCA1/2) mutation has been reported and the use of poly(ADP-ribose) polymerase inhibitor (PARPi) has achieved a certain effect, with no obvious severe side effects. The frequencies and mutated types of BRCA1/2 in advanced BTCs vary among studies. BRCA1 and BRCA2 play distinct roles in the development of BTC regardless of age or gender difference. Surprisingly, some BTC patients with germline BRCA mutation can achieve better therapeutic effects than those with a somatic mutation, and patients who carry BRCA mutation are more likely to benefit from immunotherapy alone or in combination. Herein, we provide an overview of the targeted therapies in BRCA-mutant BTCs, with a particular focus on the differences between germline and somatic BRCA1/2 mutations, as well as review the current status and perspectives.
胆道癌（BTCs）是胆道系统的侵袭性肿瘤，通常在晚期诊断，预后较差。在 BTC 患者中，已报道存在种系或体细胞乳腺癌相关基因 1/2（BRCA1/2）突变，聚 ADP-核糖聚合酶抑制剂（PARPi）的使用已取得一定效果，且无明显严重副作用。BRCA1/2 在晚期 BTCs 中的频率和突变类型在不同研究中有所不同。BRCA1 和 BRCA2 在 BTC 的发生发展中发挥着不同的作用，与年龄或性别差异无关。令人惊讶的是，一些具有种系 BRCA 突变的 BTC 患者的治疗效果优于具有体细胞突变的患者，并且携带 BRCA 突变的患者更有可能从单独或联合免疫治疗中获益。本文就 BRCA 突变型 BTCs 的靶向治疗进行综述，重点关注种系和体细胞 BRCA1/2 突变的差异，并综述现状和前景。
