Published online Sep 15, 2020. doi: 10.4251/wjgo.v12.i9.957
Peer-review started: June 3, 2020
First decision: July 21, 2020
Revised: August 3, 2020
Accepted: August 25, 2020
Article in press: August 25, 2020
Published online: September 15, 2020
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.
Core Tip: In this review, we explore current findings on the Notch signalling pathway, its molecular components, its specific roles in the development and progression of cholangiocarcinma (CCA), the treatment approaches aimed at suppressing this signaling pathway, and discuss the encouraging results presented by basic science research and preclinical trials. The Notch signaling pathway is a key driver of cholangiocarcinogenesis and represents a promising therapeutic target in CCA. A wide and comprehensive understanding of the molecular mechanisms triggered by the pathway will help us explore novel therapies against CCA.