title: BRAF and MEK inhibition for the treatment of advanced BRAF mutant melanoma.
abstract: BACKGROUND
  BRAF inhibition alone has achieved unprecedented efficacy results in patients affected by BRAF-mutated advanced melanoma. Since these findings, it was postulated that dual inhibition of BRAF and other components of the RAS/RAF/MEK/ERK MAPK pathway (such as MEK) would be superior to BRAF inhibition as monotherapy. A series of recent clinical trials have confirmed this hypothesis.
  
  
  METHODS
  In this article, the biological rationale for both single and concomitant inhibitions of the MAPK pathway in BRAF mutant melanoma is provided. Moreover, available clinical data on the efficacy and toxicity of BRAF and MEK inhibition as single agents and in combination are extensively reviewed.
  
  
  CONCLUSIONS
  Dual BRAF and MEK inhibition in advanced BRAF-mutated melanoma is superior to single inhibition in terms of efficacy without significant increase in toxicity. Therefore, BRAF plus MEK inhibition is expected to supersede single-agent BRAF inhibition in these patients in the near future.
authors.affiliation: The Royal Marsden Hospital , Fulham Road SW3 6JJ, London , UK +44 20 7811 8576 ; +44 20 7811 8103 ; james.larkin@rmh.nhs.uk.
authors.forename: Juliet
authors.initials: J
authors.lastname: Richman
authors.forename: Juan
authors.initials: J
authors.lastname: Martin-Liberal
authors.forename: Stefan
authors.initials: S
authors.lastname: Diem
authors.forename: James
authors.initials: J
authors.lastname: Larkin
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D009154:Mutation; D009362:Neoplasm Metastasis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF; MAPK; MEK; NRAS; binimetinib; cobimetinib; dabrafenib; melanoma; trametinib; vemurafenib