title: Molecular mechanisms of resistance in epidermal growth factor receptor-mutant lung adenocarcinomas.
abstract: The discovery of epidermal growth factor receptor (EGFR) mutations in nonsmall cell lung cancer (NSCLC) has allowed the identification of a subset of patients whose tumours are exquisitely sensitive to EGFR tyrosine kinase inhibitors (TKIs). Despite the efficacy and superiority of EGFR TKIs over chemotherapy as first-line therapy, all patients will ultimately develop progressive disease, with a median of 9-13 months progression-free survival. A better understanding of the molecular mechanisms underlying resistance to EGFR TKIs can help design new drugs and therapeutic strategies to overcome resistance. This has been illustrated by the new generation TKIs that are effective on the T790M mutation, which is the most frequent mechanism of acquired resistance to EGFR TKIs. In this article, we will address the main molecular mechanisms of primary and acquired resistance to EGFR TKIs in EGFR-mutant NSCLC.
authors.affiliation: Thoracic Oncology Dept, Hopital Calmette, Lille University Hospital, Université Lille Nord de France, Lille, France. UMR8161, Institut de Biologie de Lille, Siric OncoLille, Universités Lille 1, Lille, France. Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute, Boston, MA, USA. Thoracic Oncology Dept, Hopital Calmette, Lille University Hospital, Université Lille Nord de France, Lille, France. UMR8161, Institut de Biologie de Lille, Siric OncoLille, Universités Lille 1, Lille, France. Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute, Boston, MA, USA. alexis.cortot@chru-lille.fr.
authors.forename: Alexis B
authors.initials: AB
authors.lastname: Cortot
authors.affiliation: Thoracic Oncology Dept, Hopital Calmette, Lille University Hospital, Université Lille Nord de France, Lille, France. UMR8161, Institut de Biologie de Lille, Siric OncoLille, Universités Lille 1, Lille, France. Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute, Boston, MA, USA.
authors.forename: Pasi A
authors.initials: PA
authors.lastname: Jänne
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D009154:Mutation; D010641:Phenotype; D010770:Phosphotransferases / Q000037:antagonists & inhibitors; D012907:Smoking
chemical_list: D010770:Phosphotransferases; D066246:ErbB Receptors