Haber Philipp K, Sia Daniela
Liver Cancer Program, Divisions of Liver Diseases, Department of Medicine, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
Discov Med. 2019 Nov-Dec;28(155):255-265.
Biliary tract cancers (BTC), which include cholangiocarcinoma (both intra- and extrahepatic) and gallbladder, represent a heterogeneous group of malignancies with relatively low-incidence and poor prognosis. Therapeutic options for BTC patients at advanced stage are severely limited and palliative chemotherapy remains the maintreatment option. In the past decade, genome profiling via next-generation sequencing of large international cohorts has paved the way for precision oncology in BTC, identifying unique molecular subtypes, recurrent mutations, and genomic rearrangements. Targeted therapies directed against some of these aberrations are currently under investigation in phase 3 clinical studies and hold great promise to improve the prognosis of this disease. Thus, in the near term, the individual molecular alterations of the disease rather than the anatomic location will likely drive the design of clinical trials. In this review, we summarize recent molecular discoveries in BTC with a special emphasis on the most promising therapeutic targets, ultimately providing an update on current and future directions in the management of this disease.
胆道癌（BTC），包括胆管癌（肝内和肝外）和胆囊癌，是一组异质性恶性肿瘤，发病率相对较低且预后较差。晚期BTC患者的治疗选择极为有限，姑息化疗仍然是主要的治疗选择。在过去十年中，通过对大型国际队列进行下一代测序的基因组分析为BTC的精准肿瘤学铺平了道路，识别出独特的分子亚型、复发性突变和基因组重排。针对其中一些异常的靶向治疗目前正在3期临床研究中进行调查，有望显著改善这种疾病的预后。因此，在短期内，该疾病的个体分子改变而非解剖位置可能会推动临床试验的设计。在这篇综述中，我们总结了BTC最近的分子发现，特别强调了最有前景的治疗靶点，最终提供了该疾病管理的当前和未来方向的最新情况。
