Vemurafenib: Background, Patterns of Resistance, and Strategies to Combat Resistance in Melanoma

Introduction: Finding an effective treatment for metastatic melanoma has posed a series of challenges. Vemurafenib, a B-RAF tyrosine kinase inhibitor, has been one of the most successful medications to date in the treatment of metastatic melanoma. B-RAF is a serine/threonine kinase that is a part of the RAS-RAF-MEK-ERK signal transduction pathway, which plays a pivotal role in cellular proliferation, differentiation, and survival. Mutations in the B-RAF protein lead to a deregulated activation of MAPK and ERK. The focus of this review article is resulting resistance to vemurafenib and its clinical implications on the treatment of metastatic melanoma. This paper aims to highlight mechanisms of vemurafenib resistance that have been observed so far and offer potential clinical approaches to overcome resistance.