Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Sep 15;12(9):957-974.
doi: 10.4251/wjgo.v12.i9.957.

Notch signalling pathway in development of cholangiocarcinoma

Bisma Rauff  1 , Arif Malik  2 , Yasir Ali Bhatti  2 , Shafiq Ahmad Chudhary  3 , Ishtiaq Qadri  4 , Shafquat Rafiq  5
Affiliations
Review

Notch signalling pathway in development of cholangiocarcinoma

Bisma Rauff et al. World J Gastrointest Oncol. .

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; Cholangiocytes; Gamma secretase inhibitor; Notch receptors; Notch signalling pathway; Therapeutic targets.

PubMed Disclaimer

Conflict of interest statement

Conflict-of-interest statement: The authors declare no potential financial interests.

Figures

Figure 1
Figure 1
The pathway activation of Notch signalling receptors and their downstream signalling molecules.
See this image and copyright information in PMC

References

    1. Kirstein MM, Vogel A. Epidemiology and Risk Factors of Cholangiocarcinoma. Visc Med. 2016;32:395–400. - PMC - PubMed
    1. Blechacz B, Komuta M, Roskams T, Gores GJ. Clinical diagnosis and staging of cholangiocarcinoma. Nat Rev Gastroenterol Hepatol. 2011;8:512–522. - PMC - PubMed
    1. Ghouri YA, Mian I, Blechacz B. Cancer review: cholangiocarcinoma. Journal of carcinogenesis. 2015 - PMC - PubMed
    1. Everhart JE, Ruhl CE. Burden of digestive diseases in the United States Part III: Liver, biliary tract, and pancreas. Gastroenterology. 2009;136:1134–1144. - PubMed
    1. National Cancer Intelligence Network. National Cancer Intelligence Network Rare and less common Cancers, Incidence and Mortality in England, 2010 to 2013. UK: Public Health England.