The potential of PARP inhibitors in neuro-oncology.

DNA damaging agents have an integral role in the treatment of brain tumors. Recent advances in our understanding of how cancer cells repair DNA damage have made it possible to consider modification of the DNA damage response as a way in which resistance to radiotherapy and chemotherapy might be overcome. PARP inhibitors are potent but nontoxic drugs that inhibit repair of DNA single-strand breaks and increase the cytotoxic effects of radiotherapy and alkylating chemotherapy agents, including temozolomide. PARP inhibitors have potential applications in neuro-oncology because there is increasing evidence that their radio- and chemo-sensitizing effects are tumor specific. This review explores the mechanisms of action of PARP inhibitors and describes their putative mechanisms of radio- and chemo-sensitization in the context of CNS oncology. The authors go on to review their development in recent clinical trials, with a focus on glioblastoma.