title: BRAF as a therapeutic target: a patent review (2006 - 2012).
abstract: BACKGROUND
  After its identification as an oncogene in 2002, mutant BRAF has become the target of a number of drug discovery programmes, primarily aimed at the treatment of late stage or unresectable melanoma. Some of the drugs thus developed, such as vemurafenib and dabrafenib, show impressive responses in melanoma patients harbouring a BRAF mutation.
  
  
  METHODS
  This review summarises the patent literature on BRAF from 2006 to 2012, focusing on the specific areas of inhibitors of mutant BRAF, drug combinations including BRAF inhibitors, diagnostic methods for use with mutant BRAF inhibitors & diagnosis and treatment of mutant BRAF cancers resistant to BRAF inhibitors.
  
  
  CONCLUSIONS
  Whilst these first-generation BRAF inhibitors initially mediate excellent responses in late stage or unresectable melanoma patients bearing the V600 mutation, resistance usually occurs and patients eventually relapse. The patent literature for new BRAF inhibitors and therapies reflects the desire to develop second-generation drugs able to overcome this resistance and combination treatments that increase the efficiency of current mutant BRAF inhibitors.
authors.affiliation: The Institute of Cancer Research, Cancer Research UK Cancer Therapeutics Unit, Division of Cancer Therapeutics, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Zambon
authors.forename: Dan
authors.initials: D
authors.lastname: Niculescu-Duvaz
authors.forename: Ion
authors.initials: I
authors.lastname: Niculescu-Duvaz
authors.forename: Richard
authors.initials: R
authors.lastname: Marais
authors.forename: Caroline J
authors.initials: CJ
authors.lastname: Springer
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use*; D015195:Drug Design; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D006801:Humans; D015394:Molecular Structure; D058990:Molecular Targeted Therapy; D009154:Mutation; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D010330:Patents as Topic; D018579:Patient Selection; D057285:Precision Medicine; D011237:Predictive Value of Tests; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000627:therapeutic use*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf