The Molecular Biology and Treatment of Malignant Melanoma with BRAFV600 Mutations

Abstract

Since 2011, the treatment options for metastatic malignant melanoma have significantly changed. In that year, ipilimumab, an anti-CTLA4 monoclonal antibody, and vemurafenib, a potent inhibitor of mutated-BRAF (V600E and V600K), were approved by the U.S. Food and Drug Administration (FDA). In 2013, dabrafenib, another inhibitor of mutated-BRAF, and trametinib, a MEK inhibitor, were approved by the FDA. Most recently, combination therapy with dabrafenib and trametinib was approved. This article will describe a patient with metastatic malignant melanoma with BRAFV600E who has responded very well to vemurafenib monotherapy. We will then explore the molecular basis, pharmacologic development and clinical outcomes of inhibition of the mitogen-activated protein (MAP) kinase pathway in patients with metastatic malignant melanoma with oncogenic BRAF (V600E and V600K).

Keywords

• melanoma
• targeted therapy
• mutation
• mitogen-activated protein kinase