title: Acquired resistance to targeted therapies against oncogene-driven non-small-cell lung cancer: approach to subtyping progressive disease and clinical implications.
abstract: In the emerging era of targeted therapy for advanced-stage non-small-cell lung cancer, it is becoming increasingly important to anticipate underlying driver oncogene alterations at the time of initial diagnosis and tumor-tissue acquisition, so that patients can be selected in a timely fashion for first-line tyrosine kinase inhibitor (TKI) therapy if their cancers are found to harbor tyrosine-kinase-activating mutations in the epidermal growth factor receptor gene or gain-of-function rearrangements in the anaplastic lymphoma kinase gene. However, despite the clear benefits of TKI therapy over chemotherapy in these settings, the eventual emergence of acquired resistance and progressive disease (PD) is universal. How to best approach oncogene-driven non-small-cell lung cancer at the time of acquired resistance to initial TKI therapy is an increasingly complex question because of variability in mechanisms of resistance, extent of PD, and inter- and intrapatient tumor heterogeneity. Here we propose an approach to subtyping PD in the setting of acquired resistance as well as subsequent clinical implications.
authors.affiliation: Division of Hematology and Oncology, University of California, Davis, Sacramento, CA. Electronic address: david.gandara@ucdmc.ucdavis.edu.
authors.forename: David R
authors.initials: DR
authors.lastname: Gandara
authors.affiliation: Division of Hematology and Oncology, University of California, Davis, Sacramento, CA.
authors.forename: Tianhong
authors.initials: T
authors.lastname: Li
authors.affiliation: Division of Hematology and Oncology, University of California, Davis, Sacramento, CA.
authors.forename: Primo N
authors.initials: PN
authors.lastname: Lara
authors.affiliation: Division of Hematology and Oncology, University of California, Davis, Sacramento, CA.
authors.forename: Karen
authors.initials: K
authors.lastname: Kelly
authors.affiliation: Division of Hematology and Oncology, University of California, Davis, Sacramento, CA.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Riess
authors.affiliation: Fred Hutchinson Cancer Research Center, Seatlle, WA.
authors.forename: Mary W
authors.initials: MW
authors.lastname: Redman
authors.affiliation: Division of Hematology and Oncology, University of California, Davis, Sacramento, CA.
authors.forename: Philip C
authors.initials: PC
authors.lastname: Mack
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000145:classification* / Q000188:drug therapy / Q000473:pathology; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008175:Lung Neoplasms / Q000145:classification* / Q000188:drug therapy / Q000473:pathology; D009857:Oncogenes / Q000187:drug effects* / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases