Advances in using PARP inhibitors to treat cancer (BMC Medicine)

The poly (ADP-ribose) polymerase (PARP) family of enzymes plays a critical role in the maintenance of DNA integrity as part of the base excision pathway of DNA repair. A series of new therapeutic agents that are potent inhibitors of the PARP1 and PARP2 isoforms have demonstrated important clinical activity in patients with breast or ovarian cancers that are caused by mutations in either the BRCA1 or 2 genes. Significant current interest in the results of these studies is associated with the possibility that they may define a new therapeutic paradigm, wherein simultaneous loss of the capacity to repair DNA damage along several distinct pathways, due to combinations of germ line or pharmacologic DNA repair pathway inhibition, may have antitumor activity in itself, as well as enhancing the antineoplastic potential of a wide variety of current cytotoxic chemotherapeutic agents.