Therapeutic targets in melanoma: map kinase pathway.
Recent progress in our understanding of the genetic alterations that occur in the pathogenesis of melanoma provides exciting opportunities for therapy. The most important signaling pathways in melanoma lie downstream of NRAS: the RAS-BRAF-MAPK pathway. A great deal of attention has been focused on the high mutation rate in the BRAF oncogene, which approaches 60%, because BRAF itself is an appealing drug substrate and because of the central contribution of BRAF function to melanoma development that the mutation rate signifies. Agents that specifically target BRAF, such as sorafenib, as well as new molecules that function both upstream and downstream of BRAF, are being actively investigated.
Haluska
Frank G
FG
Cancer Center and Division of Hematology/Oncology, Tufts New England Medical Center, Boston, MA 02111, USA. Fhaluska@tufts-nemc.org
Ibrahim
Nageatte
N
D004359:Drug Therapy, Combination; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000235:genetics; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D018631:ras Proteins / Q000037:antagonists & inhibitors / Q000235:genetics
D047428:Protein Kinase Inhibitors; D048493:Proto-Oncogene Proteins B-raf; D020929:Mitogen-Activated Protein Kinase Kinases; D018631:ras Proteins