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Nat Rev Clin Oncol. 2012 Feb 14;9(3):144-55. doi: 10.1038/nrclinonc.2012.3.

The potential of exploiting DNA-repair defects for optimizing lung cancer treatment.

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INSERM U981, Department of Medicine, Université Paris-Sud XI-Institut Gustave Roussy, 114 rue Edouard Vaillant, 94805 Villejuif, France.


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.

[Indexed for MEDLINE]

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