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Role of PARP Inhibitors in Cancer Biology and Therapy

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Abstract:

Deeper understanding of DNA repair mechanisms and their potential value as therapeutic targets in oncology heralded the clinical development of poly(ADP-ribose) polymerase (PARP) inhibitors. Although initially developed to exploit synthetic lethality in models of cancer associated with defective DNA repair, our burgeoning knowledge of PARP biology has resulted in these agents being exploited both in cancer with select chemotherapeutic agents and in non-malignant diseases. In this review article, we briefly review the mechanisms of DNA repair and pre-clinical development of PARP inhibitors before discussing the clinical development of the various PARP inhibitors in depth.

Keywords: BRCA1; BRCA2; Base excision repair (BER); CEP-9722; DNA repair; GPI-21016; INO-1001; LT-673; MK-4827; iniparib; olaparib; poly(ADP-ribose) polymerase (PARP) inhibitors; rucaparib; synthetic lethality; triple negative breast cancer; veliparib

Document Type: Research Article

DOI: https://doi.org/10.2174/092986712802002464

Publication date: 2012-08-01

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