Keywords
BRAF mutation; BRAF inhibitors; Resistance to BRAF inhibitors
Abstract
The discovery of the driver mutation BRAF in melanoma has led to the emergence of new therapeutic treatments resulting in prolonged survival. By combining BRAF inhibitors with MEK inhibitors, median Overall Survival (OS) for patients with metastatic disease is approximately 2 years, which is an improvement by nearly a year and a half over previous therapies. Unfortunately, over 90% of patients will ultimately develop resistance to the targeted therapies and experience disease progression. Several mechanisms of resistance have been identified, including mutant BRAF allele amplification, BRAF splice variation, and activation of MEK1/2. These mechanisms are the focus of intensive research as new drugs emerge to potentially overcome resistance. This review focuses on the discovery of the BRAF mutation, the development of combination targeted therapy, the emergence of resistance to these targeted therapies, and new drugs in development to overcome this resistance
Citation
Pilat MJ, Bumma N, Back JB, Pandit T and Weise AM. BRAF: From Discovery to Drug Resistance. SM J Sarcoma Res. 2018; 2(1): 1007.