title: Targeting the MEK signaling pathway in non-small cell lung cancer (NSCLC) patients with RAS aberrations.
abstract: With the advancement in understanding the biology of non-small cell lung cancer (NSCLC), therapies focused on novel molecular pathways have come to the forefront of NSCLC treatment. This review focuses on the preclinical and clinical aspects underlying the targeting of RAS aberrations in NSCLC with special focus on MEK inhibitors which work by inhibiting the principal downstream mediator of RAS aberrations with a view on how to optimize outcomes with these agents. Preclinical evidence of the activity of MEK inhibitors in KRAS-mutant NSCLC has pushed forward the clinical development of these agents (namely selumetinib and trametinib) in KRAS-mutant NSCLC particularly in combination with other agents. A number of randomized studies have been launched to confirm the activity of these agents and to establish their position in the treatment armamentarium of NSCLC.
authors.affiliation: Clinical Oncology Department, Faculty of Medicine, Ain Shams University, Lotfy Elsayed Street, PO Box 113331, Cairo, Egypt omar.abdelrhman@med.asu.edu.eg.
authors.forename: Omar
authors.initials: O
authors.lastname: Abdel-Rahman
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D015195:Drug Design; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D058990:Molecular Targeted Therapy; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D016032:Randomized Controlled Trials as Topic
chemical_list: D000970:Antineoplastic Agents; C117307:KRAS protein, human; D047428:Protein Kinase Inhibitors; D016283:Proto-Oncogene Proteins p21(ras)
keywords: KRAS; MEK; lung cancer; selumetinib; trametinib