Poly(ADP-ribosyl)ation polymerases: mechanism and new target of anticancer therapy

Expert Review of Anticancer Therapy
Florian HeitzAndreas du Bois

Abstract

Poly(ADP-ribose)polymerase (PARP) is a ubiquitously present nuclear enzyme that is not only involved in many important cellular pathways but also contributes to chromosomal structure and genomic stability. The development of highly selective and potent PARP inhibitors has become of increasing clinical interest because of their promising efficacy in patients with breast or ovarian cancer. Furthermore, recent Phase I and Phase II trials have demonstrated that PARP inhibitors have low toxicity rates. In particular patients with either deficiency or dysfunction of BRCA, which is involved in DNA double strand break repair, appear to benefit from PARP inhibition. This article summarizes the present knowledge regarding the physiological function of PARP and ([poly]ADP-ribose) PAR, the functional product of PARP, the development of PARP inhibitors, the recent clinical data of PARP inhibitors in cancer treatment and the selection of patients who may benefit from PARP inhibition.

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Citations

Jun 5, 2012·Frontiers of Medicine·Zhifeng WangCaixia Guo
Aug 24, 2011·Cellular and Molecular Life Sciences : CMLS·Rebecca S LambSachin Teotia
Sep 16, 2011·Expert Review of Anticancer Therapy·Sheeba IrshadAndrew Tutt
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