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Lookup NU author(s): Dr Yvette DrewORCiD, Professor Ruth Plummer
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The abundant nuclear enzyme poly(ADP-ribose)polymerase-1 (PARP-1) represents an important novel target in cancer therapy. PARP-1 is essential to the repair of single strand DNA breaks via the base excision repair pathway. Inhibitors of PARP-1 have been shown to enhance the cytotoxic effects of ionising radiation and DNA damaging chemotherapy agents such as the methylating agents and topoisomerase-I inhibitors. There are currently at least eight PARP inhibitors in clinical trial development. in vitro data, in vivo preclinical data and most recently early clinical trial data suggests that PARP inhibitors could be used not only as chemo/radiotherapy sensitizers but also as single agents to selectively kill cancers defective in DNA repair, specifically cancers with mutations in the breast cancer associated (BRCA)1 and BRCA2 genes. This theory of selectively exploiting cells defective in one DNA repair pathway by inhibiting another is a major breakthrough in the treatment of cancer. The current clinical data are discussed within this review with reference to the preclinical models which predicted activity and also future directions and the possible dangers/pitfalls of this clinical strategy are explored. (C) 2009 Elsevier Ltd. All rights reserved.
Author(s): Drew Y, Plummer R
Publication type: Review
Publication status: Published
Journal: Drug Resistance Updates
Year: 2009
Volume: 12
Issue: 6
Pages: 153-156
ISSN (print): 1368-7646
ISSN (electronic): 1532-2084
URL: http://dx.doi.org/10.1016/j.drup.2009.10.001
DOI: 10.1016/j.drup.2009.10.001
