title: B-RAF inhibitors: an evolving role in the therapy of malignant melanoma.
abstract: Immunotherapy and chemotherapy benefit few patients with metastatic melanoma, and even fewer experience durable survival benefit. These poor results come from treating melanoma as a single homogeneous disease. Recently, it has been shown that targeting activated tyrosine kinases (oncogenes) can mediate striking clinical benefits in several cancers. In 2002, a mutation at the V600E amino acid of the BRAF serine/threonine kinase was described as present in over 50% of melanomas. The mutation appeared to confer a dependency by the melanoma cancer cell on its activation of the MAP kinase pathway. The frequency and specificity of this mutation (95% at V600E of BRAF) suggests that it may be a potential target for therapy, and recent results with one inhibitor, PLX4032/RG7204, bare this out. This review updates the status of BRAF inhibitors in melanoma and what may be on the horizon.
authors.affiliation: Vanderbilt University Medical Center, 1211 Medical Center Drive, Nashville, TN 37232, USA. cynthia.shepherd@vanderbilt.edu
authors.forename: Cynthia
authors.initials: C
authors.lastname: Shepherd
authors.forename: Igor
authors.initials: I
authors.lastname: Puzanov
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Sosman
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf