title: Clinical approaches to treat patients with non-small cell lung cancer and epidermal growth factor receptor tyrosine kinase inhibitor acquired resistance.
abstract: The discovery of epidermal growth factor receptor activating mutations (EGFR Mut+) has determined a paradigm shift in the treatment of non-small cell lung cancer (NSCLC). In several phase III studies, patients with NSCLC EGFR Mut+ achieved a significantly better progression-free survival when treated with a first- (gefitinib, erlotinib) or second-generation (afatinib) EGFR tyrosine kinase inhibitor (TKI) compared with standard chemotherapy. However, despite these impressive results, most patients with NSCLC EGFR Mut+ develop acquired resistance to TKIs. This review will discuss both the mechanisms of resistance to TKIs and the therapeutic strategies to overcome resistance, including emerging data on third-generation TKIs.
authors.affiliation: Unit of Medical Oncology, Department of Onco-Hematology, IRCCS, Centro di Riferimento Oncologico della Basilicata, via Padre Pio 1, 85028 Rionero in Vulture (PZ), Italy tarta1@virgilio.it.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Tartarone
authors.affiliation: Hospital Pharmacy, IRCCS, Centro di Riferimento Oncologico della Basilicata, Rionero in Vulture (PZ), Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Lerose
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors
keywords: AZD9291; CO-1686; HM61713; T790M mutation; epidermal growth factor receptor activating mutations; non-small cell lung cancer; tyrosine kinase inhibitors