BRAF kinase inhibitors for treatment of melanoma: developments from early-stage animal studies to Phase II clinical trials

Abstract

Introduction: Approximately, 30.4–66.0% of cutaneous melanomas possess a mutation in the BRAF gene that activates downstream signaling through the mitogen-activated protein (MAP) kinase pathway; this provides an attractive target for the treatment of advanced melanoma. Although BRAF inhibitors rapidly suppress melanoma growth, median progression-free survival remains unsatisfactory. Recent clinical trials have investigated drugs that can optimally enhance and prolong the anti-melanoma effects of BRAF inhibitors. Area covered: This review discusses the development of BRAF inhibitor-based combination therapies for BRAF-mutant advanced melanoma. Expert opinion: Future strategies for the treatment of advanced melanoma include novel combination therapies using BRAF/MEK inhibitors and immune checkpoints inhibitors or histone deacetylase inhibitors. These combination therapies might enhance antitumor responses against melanoma, prolonging survival in advanced melanoma patients. Further clinical studies are needed to optimize these novel combination therapies.