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J Clin Oncol. 2008 Aug 1;26(22):3785-90. doi: 10.1200/JCO.2008.16.0812. Epub 2008 Jun 30.

A synthetic lethal therapeutic approach: poly(ADP) ribose polymerase inhibitors for the treatment of cancers deficient in DNA double-strand break repair.

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1
Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, United Kingdom. alan.ashworth@icr.ac.uk

Abstract

Cancer cells frequently harbor defects in DNA repair pathways, leading to genomic instability. This can foster tumorigenesis but also provides a weakness in the tumor that can be exploited therapeutically. Tumors with compromised ability to repair double-strand DNA breaks by homologous recombination, including those with defects in BRCA1 and BRCA2, are highly sensitive to blockade of the repair of DNA single-strand breaks via the inhibition of the enzyme poly(ADP) ribose polymerase. This provides the basis for a novel synthetic lethal approach to cancer therapy.

PMID:
18591545
DOI:
10.1200/JCO.2008.16.0812
[Indexed for MEDLINE]
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