Review Article

Notch Signalling Pathways and Their Importance in the Treatment of Cancers

Author(s): Seong Lin Teoh and Srijit Das*

Volume 19 , Issue 2 , 2018

Page: [128 - 143] Pages: 16

DOI: 10.2174/1389450118666170309143419

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Abstract

Background: The Notch pathway is an evolutionarily conserved, intercellular signalling system which is present in all multicellular organisms and mammals. The Notch pathway plays an important role in the embryonic development as it controls cell proliferation, cell differentiation and binary cell fate decisions.

Objective: In the present review, we highlight the Notch signalling pathway components i.e. Notch receptors, ligands, effector, and their regulators. We also discuss the tumor biology of the Notch pathway involved in various cancers.

Results: Interestingly, the Notch signalling pathway is dysregulated in many cancers. Notch may serve as oncogene or tumor suppressor and plays an important role in cancers of the liver, pancreas, endometrium of uterus, ovary, prostate, bladder and colon. The activation of Notch pathway plays a vital role in the progression of some cancer. In addition, Notch pathway activation was also shown to drive chemoresistance in cancer, as well. Chemotherapeutically, combined NOTCH1 inhibitor synergistically attenuated chemotherapy-enriched cancer stem cell population both in vitro and in vivo. This may prove to be beneficial in the treatment of cancer.

Conclusion: The Notch inhibitors possess anti-proliferative effects on cancer, thereby serving as a new treatment for cancer.

Keywords: Notch pathway, inhibitors, signalling, cancer, treatment, embryonic development, cell proliferation.

Graphical Abstract

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