From the Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute/National Institutes of Health, Bethesda, Maryland
Author's disclosure of potential conflicts of interest is found at the end of this article.
Address reprint requests to Yves Pommier, MD, PhD, National Cancer Institute/National Institutes of Health, Bethesda, MD 20892; e-mail: pommier{at}nih.gov
Overview: DNA-damaging agents constitute a large fraction of the anticancer armamentarium (including radiation and small molecules). It also is becoming increasingly clear that DNA repair defects and defects in DNA damage response (DDR) cause cancer and are common in cancer cells. These defects probably account for the selectivity of systemically administered anticancer agents toward cancer cells. This article reviews the DNA repair and DDR defects most commonly associated with human cancer, as well as the various DNA repair pathways elicited by the anticancer agents and the currently available inhibitors that interfere with those pathways. The rational approaches for using DNA repair and DDR inhibitors based on the specific tumor defects (conditional/synthetic lethality) and examples for rational development of combination therapies also are reviewed
