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Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Sep 15, 2020; 12(9): 957-974
Published online Sep 15, 2020. doi: 10.4251/wjgo.v12.i9.957
Notch signalling pathway in development of cholangiocarcinoma
Bisma Rauff, Arif Malik, Yasir Ali Bhatti, Shafiq Ahmad Chudhary, Ishtiaq Qadri, Shafquat Rafiq
Bisma Rauff, Arif Malik, Yasir Ali Bhatti, Institute of Molecular Biology and Biotechnology, University of Lahore, Lahore 54000, Pakistan
Shafiq Ahmad Chudhary, Institute of Biomedical and Allied Health Sciences, University of Health Sciences, Lahore 54000, Pakistan
Ishtiaq Qadri, Department of Biology, Faculty of Science, King Abdulaziz University Jeddah Kingdom of Saudi Arabia
Shafquat Rafiq, Department of Gastrointestinal medicine, Croydon University Hospital, Croydon CR7 7YE, United Kingdom
Author contributions: Rauff B drafted the manuscript; Rauff B, Malik A and Bhatti YA did the literature search; Chudhrary SA provided the image; and Tables, Qadri I and Rafiq S critically reviewed the review.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Bisma Rauff, PhD, Assistant Professor, Institute of Molecular Biology and Biotechnology, University of Lahore, 1-Km Defence Road, Near Bhuptian Chowk, Lahore 54000, Pakistan. bisma.rauff@imbb.uol.edu.pk
Received: June 3, 2020
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
Processing time: 98 Days and 22 Hours
Abstract

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.

Keywords: Cholangicarcinoma; Notch receptors; Therapeutic targets; Notch signalling pathway; Gamma secretase inhibitor; Cholangiocytes

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.