Sandhu, S. K., Yap, T. A., de Bono, J. S. (2010) Poly(ADP-ribose) polymerase inhibitors in cancer treatment: A clinical perspective. EUROPEAN JOURNAL OF CANCER, 46 (1). pp. 9-20. ISSN 0959-8049

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Abstract

Inbuilt mechanisms of DNA surveillance and repair are integral to the maintenance of genomic stability. Poly(ADP-ribose) polymerase (PARP) is a nuclear enzyme that plays a critical role in DNA damage response processes. PARP inhibition has been successfully employed as a novel therapeutic strategy to enhance the cytotoxic effects of DNA-damaging agents. We have shown that PARP inhibition has substantial single agent antitumour activity with a wide therapeutic index in homologous DNA repair-defective tumours such as those arising in BRCA1 and BRCA2 mutation carriers. This is the first successful clinical application of a synthetic lethal approach to targeting cancer. Exploitation of defects in DNA repair pathways through targeted inhibition of salvage repair pathways is an exciting anticancer approach, with potentially broad clinical applicability. Several PARP inhibitors are now in clinical development. This review outlines the biological function and rationale of targeting PARP, details pre-clinical and clinical data and discusses the promises and challenges involved in developing these antitumour agents. (C) 2009 Elsevier Ltd. All rights reserved.

Item Type:	Editorial
Authors (ICR Faculty only):	De-Bono, Johann
All Authors:	Sandhu, S. K., Yap, T. A., de Bono, J. S.
Uncontrolled Keywords:	PARP inhibitors; BRCA1; BRCA2; Homologous recombination; Single-strand break repair; Double-strand break repair;ADP-RIBOSE POLYMERASE; DOUBLE-STRAND BREAKS; DEPENDENT PROTEIN-KINASE; BRCA1 PROMOTER REGION; BASE EXCISION-REPAIR; DNA-REPAIR; HOMOLOGOUS RECOMBINATION; MUTATION CARRIERS; PARP INHIBITORS; THERAPEUTIC STRATEGY
Research teams:	ICR divisions > Cancer Therapeutics > Cancer Biomarkers ICR divisions > Clinical Studies > Cancer Biomarkers ICR divisions > Clinical Studies > Prostate Cancer Targeted Therapy Group
Depositing User:	Users 10 not found.
Date Deposited:	22 Feb 2010 10:32
Last Modified:	11 Jul 2017 10:12
URI:	http://publications.icr.ac.uk/id/eprint/9316

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