title: Irreversible EGFR inhibitors in the treatment of advanced NSCLC.
abstract: The epidermal growth factor receptor (EGFR) is among the most important targets in the treatment of advanced non-small cell lung cancer (NSCLC). Erlotinib and gefitinib, two small molecules, are reversible EGFR tyrosine kinase inhibitors (TKIs). Non-small cell lung cancers with EGFR mutations, are characterized by excellent responses when treated with the EGFR-TKIs gefitinib and erlotinib. However, all the patients with tumors harbouring EGFR mutations experience disease progression after a median of 10 to 14 months of treatment with gefitinib or erlotinib. A group of new generation EGFR-TKIs irreversibly inhibit EGFR-TK and represent one of the strategies that may potentially overcome the acquired resistance to gefitinib and erlotinib or achieve better outcomes than reversible inhibitors in the first-line treatment of EGFR mutant lung cancers. Afatinib (BIBW 2992) and PF299804 are the irreversible EGFR-TKIs with the most relevant data in the treatment of advanced NSCLC, as primary EGFR-targeted therapy and after resistance to reversible EGFR-TKIs. However, to date, the role of irreversible EGFR inhibitors remains to be defined.
authors.forename: Paolo
authors.initials: P
authors.lastname: Maione
authors.forename: Antonio
authors.initials: A
authors.lastname: Rossi
authors.forename: Marianna
authors.initials: M
authors.lastname: Bareschino
authors.forename: Paola Claudia
authors.initials: PC
authors.lastname: Sacco
authors.forename: Clorinda
authors.initials: C
authors.lastname: Schettino
authors.forename: Francesca
authors.initials: F
authors.lastname: Casaluce
authors.forename: Assunta
authors.initials: A
authors.lastname: Sgambato
authors.affiliation: Division of Medical Oncology, "S.G. Moscati" Hospital, Contrada Amoretta - 83100 Avellino Italy. pmaione@libero.it.
authors.forename: Cesare
authors.initials: C
authors.lastname: Gridelli
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*
chemical_list: D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors