title: The potential of exploiting DNA-repair defects for optimizing lung cancer treatment.
abstract: The tumor genome is commonly aberrant as a consequence of mutagenic insult and incomplete DNA repair. DNA repair as a therapeutic target has recently received considerable attention owing to the promise of drugs that target tumor-specific DNA-repair enzymes and potentiate conventional cytotoxic therapy through mechanism-based approaches, such as synthetic lethality. Treatment for non-small-cell lung cancer (NSCLC) consists mainly of platinum-based chemotherapy regimens and improvements are urgently needed. Optimizing treatment according to tumor status for DNA-repair biomarkers, such as ERCC1, BRCA1 or RRM1, could predict response to platinum, taxanes and gemcitabine-based therapies, respectively, and might improve substantially the response of individual patients' tumors. Finally, recent data on germline variation in DNA-repair genes may also be informative. Here, we discuss how a molecular and functional DNA-repair classification of NSCLC may aid clinical decision making and improve patient outcome.
authors.affiliation: INSERM U981, Department of Medicine, Université Paris-Sud XI-Institut Gustave Roussy, 114 rue Edouard Vaillant, 94805 Villejuif, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Postel-Vinay
authors.forename: Elsa
authors.initials: E
authors.lastname: Vanhecke
authors.forename: Ken A
authors.initials: KA
authors.lastname: Olaussen
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Lord
authors.forename: Alan
authors.initials: A
authors.lastname: Ashworth
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Soria
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D015197:Carcinogenicity Tests; D004247:DNA / Q000032:analysis; D004260:DNA Repair / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004247:DNA