title: Targeted therapies for cutaneous melanoma.
abstract: Melanoma is resistant to cytotoxic therapy, and treatment options for advanced disease have been limited historically. However, improved understanding of melanoma driver mutations, particularly those involving the mitogen-activated protein kinase pathway, has led to the development of targeted therapies that are effective in this previously treatment-refractory disease. In cutaneous melanomas with BRAF V600 mutations the selective RAF inhibitors, vemurafenib and dabrafenib, and the MEK inhibitor, trametinib, have demonstrated survival benefits. Early signals of efficacy have also been demonstrated with MEK inhibitors in melanomas with NRAS mutations, and KIT inhibitors offer promise in melanomas driven through activation of their target receptor.
authors.affiliation: Division of Cancer Medicine and Research, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Victoria 3002, Australia; Department of Pathology, University of Melbourne, Grattan Street, Parkville, Victoria 3010, Australia. Electronic address: Damien.Kee@petermac.org.
authors.forename: Damien
authors.initials: D
authors.lastname: Kee
authors.affiliation: Division of Cancer Medicine and Research, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Victoria 3002, Australia; Department of Pathology, University of Melbourne, Grattan Street, Parkville, Victoria 3010, Australia; Department of Medicine, St Vincent Hospital, University of Melbourne, Victoria Parade, Fitzroy, Victoria 3065, Australia.
authors.forename: Grant
authors.initials: G
authors.lastname: McArthur
mesh_terms: D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D007211:Indoles / Q000627:therapeutic use; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics; D058990:Molecular Targeted Therapy / Q000379:methods*; D009154:Mutation; D010091:Oximes / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000235:genetics; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics; D013449:Sulfonamides / Q000627:therapeutic use; D016019:Survival Analysis; D000077484:Vemurafenib
chemical_list: D007093:Imidazoles; D007211:Indoles; D010091:Oximes; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D000077484:Vemurafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C561627:dabrafenib
keywords: BRAF; MAPK signaling; MEK; Melanoma; NRAS; Targeted therapy