title: Selumetinib (AZD6244; ARRY-142886)  in the treatment of metastatic melanoma.
abstract: BACKGROUND
  Melanoma is the fifth most common cancer in men and seventh most common in women in the USA, and prognosis for patients with advanced melanoma is poor. The mitogen-activated protein (MAP) kinase signaling pathway is essential for proliferation and survival of melanoma cells. Effective inhibition of MAP kinase kinase (MEK) protein has been shown to downregulate the MAP kinase pathway, resulting in melanoma cell growth arrest and apoptosis. Selumetinib is an orally available, selective non-ATP-competitive MEK1 and MEK2 inhibitor.
  
  
  METHODS
  In this review, the authors discuss the rationale for MEK inhibition therapy in melanoma and summarize data from the preclinical and clinical studies of selumetinib for advanced melanoma.
  
  
  CONCLUSIONS
  As a majority of advanced melanomas have an activated MAP kinase signal transduction pathway, there is a strong preclinical rationale for investigating selumetinib in patients with metastatic melanoma. The results of early clinical studies of selumetinib suggest that selumetinib may have a role in melanoma therapy, especially in certain subsets of patients, such as those whose tumor harbors a BRAF mutation. Current studies of selumetinib are addressing the efficacy of selumetinib in these patients.
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Sapna P
authors.initials: SP
authors.lastname: Patel
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Kim
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology* / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009362:Neoplasm Metastasis; D016032:Randomized Controlled Trials as Topic; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C517975:AZD 6244; D001562:Benzimidazoles; D020929:Mitogen-Activated Protein Kinase Kinases