title: Targeted therapy in melanoma.
abstract: Since the discovery of activating mutations in the BRAF oncogene in melanoma, there has been remarkable progress in the development of targeted therapies for unresectable and metastatic melanoma. We review the latest developments in our understanding of the role of BRAF/MEK/ERK pathway signaling in melanoma, and the development of inhibitors of this pathway. We also explore alternative mutations seen in melanoma, such as NRAS, KIT, GNAQ, and GNA11, and the drug development that is ongoing based on this biology. Strategies for the management of the vexing clinical problem of BRAF inhibitor resistance, primarily via combination therapy, are outlined. With the recent approval of the BRAF inhibitor vemurafenib for stage IV metastatic melanoma, use of this agent is expanding in the United States. Thus, management of the skin toxicities of this agent, such as squamous cell carcinomas, "acneiform" eruptions, hand-foot syndrome, and panniculitis, will be a growing problem facing dermatologists today. We discuss the toxicities of targeted agents in use for melanoma, in particular the dermatologic effects and the management of these skin toxicities.
authors: Department of Cutaneous Oncology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, USA.
authors: Ragini R
authors: RR
authors: Kudchadkar
authors: Keiran S M
authors: KS
authors: Smalley
authors: L Frank
authors: LF
authors: Glass
authors: James S
authors: JS
authors: Trimble
authors: Vernon K
authors: VK
authors: Sondak
mesh_terms: D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D020930:MAP Kinase Kinase Kinases / Q000502:physiology; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D058990:Molecular Targeted Therapy; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000502:physiology; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D013449:Sulfonamides / Q000627:therapeutic use; D000077484:Vemurafenib
chemical_list: D007211:Indoles; D013449:Sulfonamides; D000077484:Vemurafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D048049:Extracellular Signal-Regulated MAP Kinases; D020930:MAP Kinase Kinase Kinases