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Targeting Poly(ADP-Ribose) Polymerase: A Two-Armed Strategy for Cancer Therapy

Authors' Affiliation: Northern Institute for Cancer Research, Newcastle University, United Kingdom

Requests for reprints: Elizabeth Ruth Plummer, Northern Institute for Cancer Research, Medical School, Newcastle University, Paul O'Gorman Building, Framlington Place, Newcastle upon Tyne, UNE2 4HH United Kingdom. Phone: 44-191-246-4414; E-mail: e.r.plummer{at}ncl.ac.uk.

Abstract

The DNA repair pathways are protective of the host genome in normal cells; however, in cancer cells, these pathways may be disrupted and predispose to tumorigenesis or their activity may overcome the potentially cytotoxic damage caused by anticancer agents and be a mechanism of resistance. Poly(ADP-ribose) polymerase inhibitors, which block base excision repair of single-strand breaks, have entered the clinic in the last few years. This article discusses the interactions between the pathways of single- and double-strand break repair, which explain the two clinical development strategies for this class of drugs.

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