Department of Pathology, Center for Investigation in Translational Oncology (CITO), School of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile.
Department of Pathology, School of Medicine, Universidad de La Frontera, CEGIN-BIOREN, Temuco 4811230, Chile.
Cancer Treat Rev. 2015 Mar;41(3):222-34. doi: 10.1016/j.ctrv.2015.01.003. Epub 2015 Jan 20.
Gallbladder cancer is the most common and aggressive malignancy of the biliary tract. The complete surgical resection is the only potentially curative approach in early stage; however, most cases are diagnosed in advanced stages and the response to traditional chemotherapy and radiotherapy is extremely limited, with modest impact in overall survival. The recent progress in understanding the molecular alterations of gallbladder cancer has shown great promise for the development of more effective treatment strategies. This has mainly resulted from the identification of molecular alterations in relevant intracellular signaling pathways-Hedgehog, PI3K/AKT/mTOR, Notch, ErbB, MAPK and angiogenesis-which are potential tailored targets for gallbladder cancer patients. This review discusses the recent remarkable progress in understanding the molecular alterations that represent novel prognosis molecular markers and therapeutic targets for gallbladder cancer, which will provide opportunities for research and for developing innovative strategies that may enhance the benefit of conventional chemotherapy, or eventually modify the fatal natural history of this orphan disease.
胆囊癌是胆道系统最常见和侵袭性最强的恶性肿瘤。在早期阶段，完全手术切除是唯一可能治愈的方法；然而，大多数病例在晚期诊断，传统化疗和放疗的反应非常有限，对总生存率的影响不大。近年来对胆囊癌分子改变的认识取得了很大的进展，为开发更有效的治疗策略带来了希望。这主要是由于确定了相关细胞内信号通路（Hedgehog、PI3K/AKT/mTOR、Notch、ErbB、MAPK 和血管生成）中的分子改变，这些改变可能成为胆囊癌患者的潜在靶向治疗靶点。本文综述了近年来在理解代表胆囊癌新型预后分子标志物和治疗靶点的分子改变方面的显著进展，这将为研究和开发创新策略提供机会，这些策略可能增强传统化疗的疗效，或最终改变这种孤儿病的致命自然病程。
