title: The role of mitogen-activated protein targeting in melanoma beyond BRAFV600.
abstract: OBJECTIVE
  Targeted therapy in melanoma is well established for patients with tumors harboring BRAF mutations, but less so for other molecularly defined subsets. In this review, emerging preclinical, genomic, and early clinical data are discussed regarding the use of mitogen-activated protein (MAPK) pathway inhibitors in other molecular subsets of melanoma.
  
  
  RESULTS
  There are now four well defined subsets of melanoma based on The Cancer Genome Atlas: BRAF driven, NRAS driven, NF1 mutant, and 'triple wild type'. The former three subtypes predict signaling through the MAPK pathway and sensitivity to inhibitors of this pathway's mediators. With ongoing translation of preclinical findings into clinical trials, there is great hope that these strategies will improve the care of patients who fall into these other molecular subsets.
  
  
  CONCLUSIONS
  A more comprehensive understanding of genetically defined subtypes of melanoma is emerging. Efforts in the clinic are already underway, but additional, well designed trials of MAPK-targeted therapy planned and needed.
authors: Center for Melanoma, Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA.
authors: Ryan J
authors: RJ
authors: Sullivan
mesh_terms: D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors*; D020558:GTP Phosphohydrolases / Q000235:genetics; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008545:Melanoma / Q000188:drug therapy*; D008565:Membrane Proteins / Q000235:genetics; D058990:Molecular Targeted Therapy / Q000379:methods*; D009154:Mutation / Q000235:genetics; D025542:Neurofibromin 1 / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000235:genetics; D012878:Skin Neoplasms / Q000188:drug therapy*
chemical_list: D008565:Membrane Proteins; D025542:Neurofibromin 1; D047428:Protein Kinase Inhibitors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D048049:Extracellular Signal-Regulated MAP Kinases; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human