Systemic review on B-RafV600E mutation as potential therapeutic target for the treatment of cancer

Abstract

Cancer is one of the major public catastrophes worldwide and as per WHO, cancer is the leading cause of death universally after CVS disorders accounting for 9.6 million deaths in 2018. WHO statistics revealed five dangerous types of cancer viz. lung, breast, colorectal, prostate and skin. In male, lung cancer causes highest death, while in female, breast cancer causes the most. Alteration in MAPK signalling pathway plays a significant role in majority of cancer cases. Raf protein is activated by phosphorylation via downstream regulation of the MAPK pathway. Raf composed of 3 subtypes, viz. A-Raf, B-Raf, and C-Raf. B-Raf kinase plays a significant role in healthy cell growth in the MAPK pathway and the problem associated with B-Raf mutation leads to the development of cancer and other diseases. The progression of mutant B-Raf (B-RafV600E) protein is higher in cancer as compare to other diseases. In 2002, B-RafV600E mutation was identified for the first time in the development of cancer. The frequency of B-RafV600E mutation is higher in melanoma, thyroid, colorectal and ovarian cancer. We have covered small molecule B-RafV600E inhibitors reported in various literatures; from 2002 to 2020 and also covered clinical trial data. To widen the scope of readers, we compiled details of small molecules, specifically inhibiting B-RafV600E mutant and showing anti-proliferative activity against various cancer cell lines along with in-vivo data. We believe that the information covered here will be important in signifying the potentials of B-RafV600E mutation and its inhibitors as potent anticancer agents.