Marks Eric I, Yee Nelson S
Eric I Marks, Department of Medicine, Penn State Milton S. Hershey Medical Center, Hershey, PA 17033, United States.
World J Gastroenterol. 2016 Jan 28;22(4):1335-47. doi: 10.3748/wjg.v22.i4.1335.
The primary malignancies of the biliary tract, cholangiocarcinoma and gallbladder cancer, often present at an advanced stage and are marginally sensitive to radiation and chemotherapy. Accumulating evidence indicates that molecularly targeted agents may provide new hope for improving treatment response in biliary tract carcinoma (BTC). In this article, we provide a critical review of the pathogenesis and genetic abnormalities of biliary tract neoplasms, in addition to discussing the current and emerging targeted therapeutics in BTC. Genetic studies of biliary tumors have identified the growth factors and receptors as well as their downstream signaling pathways that control the growth and survival of biliary epithelia. Target-specific monoclonal antibodies and small molecules inhibitors directed against the signaling pathways that drive BTC growth and invasion have been developed. Numerous clinical trials designed to test these agents as either monotherapy or in combination with conventional chemotherapy have been completed or are currently underway. Research focusing on understanding the molecular basis of biliary tumorigenesis will continue to identify for targeted therapy the key mutations that drive growth and invasion of biliary neoplasms. Additional strategies that have emerged for treating this malignant disease include targeting the epigenetic alterations of BTC and immunotherapy. By integrating targeted therapy with molecular profiles of biliary tumor, we hope to provide precision treatment for patients with malignant diseases of the biliary tract.
胆道的原发性恶性肿瘤，即胆管癌和胆囊癌，通常在晚期出现，对放疗和化疗的敏感性较低。越来越多的证据表明，分子靶向药物可能为改善胆道癌（BTC）的治疗反应带来新希望。在本文中，我们除了讨论BTC目前和新兴的靶向治疗方法外，还对胆道肿瘤的发病机制和基因异常进行了批判性综述。胆道肿瘤的基因研究已经确定了控制胆管上皮生长和存活的生长因子、受体及其下游信号通路。针对驱动BTC生长和侵袭的信号通路，已经开发出了靶点特异性单克隆抗体和小分子抑制剂。许多旨在测试这些药物作为单一疗法或与传统化疗联合使用的临床试验已经完成或正在进行。专注于理解胆道肿瘤发生分子基础的研究将继续确定驱动胆道肿瘤生长和侵袭的关键突变，以便进行靶向治疗。治疗这种恶性疾病出现的其他策略包括针对BTC的表观遗传改变和免疫治疗。通过将靶向治疗与胆道肿瘤的分子特征相结合，我们希望为胆道恶性疾病患者提供精准治疗。
