title: Vemurafenib: the road to personalized medicine in melanoma.
abstract: Advanced melanoma has a poor prognosis due to its resistance to traditional chemotherapeutics, leading to the search for alternative treatment approaches. With the finding that approximately 50% of melanomas harbor an activating mutation in the serine/threonine-protein kinase B-raf gene (BRAF), inhibition of mutated B-raf represented an attractive and innovative focus for the development of novel targeted therapy potentially benefiting a large proportion of melanoma patients. Impressive response rates with an overall survival benefit in addition to minimal treatment-related toxicity in phase I-III clinical studies led to the FDA's approval of vemurafenib for patients with locally advanced/unresectable or metastatic BRAFV600E-mutated malignant melanoma in August 2011. While the majority of patients with BRAF-mutated disease show favorable treatment responses shortly after initiation of vemurafenib therapy, the median progression-free survival is 6 months, making the search for resistance mechanisms a high priority. While vemurafenib represents an excellent model for successful targeted anticancer therapy, long-term safety data are needed and rational combination with other agents will be critical to prevent or circumvent the development of resistance.
authors.affiliation: University of Colorado Cancer Center, Aurora, CO, USA.
authors.forename: R N
authors.initials: RN
authors.lastname: Amaria
authors.forename: K D
authors.initials: KD
authors.lastname: Lewis
authors.forename: A
authors.initials: A
authors.lastname: Jimeno
mesh_terms: D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D008545:Melanoma / Q000188:drug therapy*; D009154:Mutation; D057285:Precision Medicine; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000235:genetics; D013449:Sulfonamides / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000077484:Vemurafenib
chemical_list: D007211:Indoles; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D000077484:Vemurafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf