title: Targeted Therapy for Melanoma.
abstract: Vemurafenib and dabrafenib, two potent tyrosine kinase inhibitors (TKIs) of the BRAF(V600E) kinase, are highly effective in the treatment of a BRAF (V600) -mutant metastatic melanoma. These are selective type I inhibitors (functional against the active conformation of the kinase) of the RAF kinases, which are key players in the mitogen-activated protein kinase (MAPK) pathway. BRAF (V600) mutations are present in approximately 7 % of all cancers, including high frequencies of mutations reported in 50 % of advanced melanomas and 100 % of hairy cell leukemias. As with most targeted therapies, resistance to BRAF inhibitors is an issue, and mechanisms of resistance are varied. Combining BRAF inhibitors with MEK inhibitors such as trametinib delays the development of resistance. Rationally combining targeted therapies to address the mechanism of resistance or combining BRAF inhibitors with other effective therapies such as immunotherapy may result in further improvement in outcomes for patients.
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, University of California Los Angeles (UCLA), Le Conte Avenue, Los Angeles, CA, 10833, USA.
authors.forename: Deborah J L
authors.initials: DJ
authors.lastname: Wong
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, University of California Los Angeles (UCLA), Le Conte Avenue, Los Angeles, CA, 10833, USA. aribas@mednet.ucla.edu.|Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA, USA. aribas@mednet.ucla.edu.
authors.forename: Antoni
authors.initials: A
authors.lastname: Ribas
mesh_terms: D006801:Humans; D007167:Immunotherapy; D008545:Melanoma / Q000188:drug therapy*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors*; D058990:Molecular Targeted Therapy; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D047428:Protein Kinase Inhibitors; D048493:Proto-Oncogene Proteins B-raf; D020929:Mitogen-Activated Protein Kinase Kinases
keywords: BRAF; Dabrafenib; MEK; Melanoma; Trametinib; Vemurafenib