title: Trametinib (GSK1120212) in the treatment of melanoma.
abstract: BACKGROUND
  The discovery of somatic mutations in melanoma has advanced our knowledge of the biology of the disease. The mutations, such as those in NRAS, BRAF, GNAQ and GNA11, promote the growth of melanoma cells in most part through the mitogen-activated protein kinase (MAPK) pathway. Understanding the molecular pathways of some of these mutations has resulted in the successful development of selective BRAF inhibitors. Yet, a cure for advanced melanoma is far from reality. Targeting MAPK/ERK kinase (MEK), an essential intermediary kinase protein within the MAPK pathway, may be a promising way to treat patients with BRAF or other genomic mutation.
  
  
  METHODS
  The authors discuss the MAPK pathway in melanoma and review the preclinical and clinical studies of the MEK inhibitor, trametinib , in melanoma. They also discuss the potential of using trametinib in the targeted therapy of advanced melanoma.
  
  
  CONCLUSIONS
  Studies have demonstrated the activity of trametinib in BRAF-mutant melanoma, suggesting that it could be a very reasonable alternative to BRAF inhibitors for these patients. Current clinical investigations have shown great promise with the combination of trametinib and dabrafenib in patients with BRAF-mutant melanoma; a number of clinical trials of trametinib in combination with other targeted drugs are underway.
authors: Duke University Medical Center, Division of Medical Oncology, Durham, NC, USA.
authors: April K S
authors: AK
authors: Salama
authors: Kevin B
authors: KB
authors: Kim
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008545:Melanoma / Q000188:drug therapy* / Q000201:enzymology; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D058990:Molecular Targeted Therapy; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011728:Pyridones / Q000627:therapeutic use*; D011744:Pyrimidinones / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011728:Pyridones; D011744:Pyrimidinones; C560077:trametinib; D020929:Mitogen-Activated Protein Kinase Kinases