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The potential of PARP inhibitors in genetic breast and ovarian cancers

Lookup NU author(s): Dr Yvette DrewORCiD, Professor Alan Calvert


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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 DNA single-strand breaks via the base excision repair pathway. Inhibitors of PARP-1 have been shown to enhance the cytotoxic effects of ionizing radiation and DNA damaging chemotherapy agents, such as the methylating agents and topoisomerase I inhibitors. There are currently at least five PARP inhibitors in clinical trial development. Recent in vitro and in vivo evidence suggests that PARP inhibitors could be used not only as chemo/radiotherapy sensitizers, but as single agents to selectively kill cancers defective in DNA repair, specifically cancers with mutations in the breast cancer associated (BRCA) 1 and 2 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. BRCA1/2 mutations are responsible for the majority of genetic breast/ovarian cancers, known as the hereditary breast ovarian cancer syndrome. This review summarizes the preclinical and clinical evidence for the potential of PARP inhibitors in genetic breast and ovarian cancers. © 2008 New York Academy of Sciences.

Publication metadata

Author(s): Drew, Y., Calvert, A. H.

Editor(s): Branicki, F.J.; Adem, A.; Ghazal-Aswad, S.

Publication type: Conference Proceedings (inc. Abstract)

Publication status: Published

Conference Name: Annals of the New York Academy of Sciences

Year of Conference: 2008

Number of Volumes: 1166

Pages: 136-145

Publisher: Blackwell Publishing


DOI: 10.1196/annals.1414.020

Library holdings: Search Newcastle University Library for this item

Series Title: Recent Advances in Clinical Oncology

ISBN: 9781573317009