Rauff Bisma, Malik Arif, Bhatti Yasir Ali, Chudhary Shafiq Ahmad, Qadri Ishtiaq, Rafiq Shafquat
Institute of Molecular Biology and Biotechnology, University of Lahore, Lahore 54000, Pakistan.
Institute of Biomedical and Allied Health Sciences, University of Health Sciences, Lahore 54000, Pakistan.
World J Gastrointest Oncol. 2020 Sep 15;12(9):957-974. doi: 10.4251/wjgo.v12.i9.957.
Cholangiocarcinoma (CCA) comprises of extra-hepatic cholangiocarcinoma and intrahepatic cholangiocarcinoma cancers as a result of inflammation of epithelium cell lining of the bile duct. The incidence rate is increasing dramatically worldwide with highest rates in Eastern and South Asian regions. Major risk factors involve chronic damage and inflammation of bile duct epithelium from primary sclerosing cholangitis, chronic hepatitis virus infection, gallstones and liver fluke infection. Various genetic variants have also been identified and as CCA develops on the background of biliary inflammation, diverse range of molecular mechanisms are involved in its progression. Among these, the Notch signalling pathway acts as a major driver of cholangiocarcinogenesis and its components (receptors, ligands and downstream signalling molecules) represent a promising therapeutic targets. Gamma-Secretase Inhibitors have been recognized in inhibiting the Notch pathway efficiently. A comprehensive knowledge of the molecular pathways activated by the Notch signalling cascade as well as its functional crosstalk with other signalling pathways provide better approach in developing innovative therapies against CCA.
胆管癌（CCA）由肝外胆管癌和肝内胆管癌组成，是胆管上皮细胞炎症的结果。全球范围内其发病率正在急剧上升，在东亚和南亚地区发病率最高。主要危险因素包括原发性硬化性胆管炎、慢性肝炎病毒感染、胆结石和肝吸虫感染导致的胆管上皮慢性损伤和炎症。各种基因变异也已被识别，并且由于CCA在胆管炎症背景下发生发展，其进展涉及多种分子机制。其中，Notch信号通路是胆管癌发生的主要驱动因素，其组成成分（受体、配体和下游信号分子）是有前景的治疗靶点。γ-分泌酶抑制剂已被证实能有效抑制Notch通路。全面了解Notch信号级联激活的分子途径及其与其他信号通路的功能相互作用，为开发针对CCA的创新疗法提供了更好的方法。
