Drug Overview

Zelboraf (vemurafenib; Roche/Chugai/Daiichi Sankyo) is an orally available agent that selectively targets the BRAF mutation. BRAF is part of the mitogen-activated protein kinase (MAPK) signal transduction pathway, which is critical in tumor cell proliferation. The MAPK pathway controls cell proliferation following growth receptor stimulation. The typical binding of the ligand to the receptor triggers a chain of events that includes the activation of a series of downstream effectors, one of these being the RAF series of serine/threonine kinases, including BRAF. However, melanoma cells with BRAF mutations are known to be “addicted” to BRAF, as the mutation renders the protein constitutively active, thereby eliminating the need for receptor-mediated activation, and the efficacy of Zelboraf has demonstrated the potential of BRAF inhibitor treatment.