The Role of BRAF Gene in Cancer: Literature Review and Future Directions

: The BRAF gene encodes a protein belonging to the RAF family of serine/threonine protein kinases. This protein plays an important role in regulating the MAP kinase signaling pathway, which is involved in cellular development, differentiation, division, proliferation, secretion, inflammatory responses and apoptosis in mammalian cells. Since 2002, the mutation of valine 600 to glutamic acid (V600E) is the most prevalent, and it is found to be recurrent in many cancer types. It is frequently identified cancer-causing mutation in melanoma, colorectal cancer, thyroid carcinoma, non-small cell lung carcinoma, hairy cell leukemia, non-Hodgkin lymphoma, glioneuronal tumors, hepatocellular carcinoma, adenocarcinoma of lung, ovarian cancer, and also others malignancies and some cancer metastasis. In the early 1990s, some researchers began studying MAP kinase signaling pathway involved in controlling cell growth and its role in cancer, and it helped identify targets for new classes of cancer therapy. Later BRAF mutation was found in over 50% of melanomas. The overactive BRAF protein expression looked like an attractive drug target. Elucidating the detailed molecular structure of the mutant protein helped pharmaceutical companies developed selective inhibitors of mutated BRAF, including Vemurafenib and Dabrafenib, which have been approved to treat melanoma by the Food and Drug Administration (FDA). In addition, there is a growing number of targeted agents that are being evaluated to treat various BRAF-mutant advanced cancer (especially melanoma, lung, thyroid and colorectal cancer), including other RAF kinase inhibitors and/or MEK inhibitors. the mechanisms of the resistance, therefore it will help us to understand diseases biology and continuously bringing new therapeutic strategies for melanoma and/or others malignancies, including other drugs combination and next-generation of BRAF inhibitors.