title: Selumetinib in the treatment of non-small-cell lung cancer.
abstract: The RAS-RAF-MEK-ERK pathway regulates processes involved in the proliferation and survival of cells. KRAS mutations, prevalent in approximately 30% of patients with non-small-cell lung cancer (NSCLC), result in constitutive activation of the pathway. Selumetinib (AZD6244, ARRY-142886) is a potent and selective inhibitor of MEK1/2 which has demonstrated significant efficacy in combination with docetaxel in patients with KRAS mutant pretreated advanced NSCLC. Several trials in combination with other chemotherapy and targeted therapy regimens in lung cancer are ongoing. We review the development of selumetinib in patients with NSCLC, summarize the pharmacodynamic, pharmacokinetic and tolerability characteristics, and the available clinical trial data to understand the role of selumetinib in the treatment of NSCLC.
authors.affiliation: The Christie NHS Foundation Trust, Manchester, UK.|Hospital Valme, Seville, Spain.
authors.forename: Reyes
authors.initials: R
authors.lastname: Bernabé
authors.affiliation: The Christie NHS Foundation Trust, Manchester, UK.
authors.forename: Ana
authors.initials: A
authors.lastname: Patrao
authors.affiliation: The Christie NHS Foundation Trust, Manchester, UK.
authors.forename: Louise
authors.initials: L
authors.lastname: Carter
authors.affiliation: The Christie NHS Foundation Trust, Manchester, UK.|The University of Manchester, Manchester, UK.
authors.forename: Fiona
authors.initials: F
authors.lastname: Blackhall
authors.affiliation: The Christie NHS Foundation Trust, Manchester, UK.|The University of Manchester, Manchester, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Dean
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000077143:Docetaxel; D006801:Humans; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors; D048370:MAP Kinase Kinase 2 / Q000037:antagonists & inhibitors; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D043823:Taxoids / Q000627:therapeutic use
chemical_list: C517975:AZD 6244; D001562:Benzimidazoles; C117307:KRAS protein, human; D047428:Protein Kinase Inhibitors; D043823:Taxoids; D000077143:Docetaxel; C482128:MAP2K2 protein, human; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; C482125:MAP2K1 protein, human; D016283:Proto-Oncogene Proteins p21(ras)
keywords: MEK inhibitor; non-small-cell lung cancer; selumetinib