title: The "SWOT" of BRAF inhibition in melanoma: RAF inhibitors, MEK inhibitors or both?
abstract: Activating mutations in the BRAF gene are among the most prevalent kinase mutations in human cancer. BRAF mutations are most frequent in patients with melanoma where they occur in approximately 50% of patients with advanced disease. Remarkable clinical activity has recently been reported with highly selective RAF inhibitors in melanoma patients whose tumors harbor V600E BRAF mutations. The response rates of RAF inhibitors in patients with BRAF-mutant melanomas far exceed the activity level of any prior therapy studied in this disease. The results suggest that we have entered an era of personalized therapy for patients with metastatic melanoma in which treatment selection will be guided by BRAF mutational status. This review will discuss the strengths, weaknesses, opportunities and threats ("SWOT") of developing RAF and MEK selective inhibitors as anti-cancer therapies, recent insights into the mechanisms of intrinsic and acquired resistance to these agents, and current efforts to develop mechanism-based combination therapies.
authors: Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors: Moriah H
authors: MH
authors: Nissan
authors: David B
authors: DB
authors: Solit
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors*; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics; D009154:Mutation / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012878:Skin Neoplasms / Q000188:drug therapy / Q000235:genetics; D048490:raf Kinases / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D048490:raf Kinases; D020930:MAP Kinase Kinase Kinases