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Poly(ADP-ribose)polymerase-1 (PARP-1) in carcinogenesis: potential role of PARP inhibitors in cancer treatment

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Abstract

Poly(ADP-ribose)polymerase-1 (PARP-1) is a nuclear, zinc-finger, deoxyribonucleic acid (DNA)-binding protein that detects specifically DNA strand breaks generated by different genotoxic agents. Whereas activation of PARP-1 by mild genotoxic stimuli facilitates DNA repair and cell survival, severe DNA damage triggers different pathways of cell death, including PARP-mediated cell death through the translocation of apoptosis inducing factor (AIF) from the mitochondria to the nucleus. Pharmacological inhibition or genetic ablation of PARP-1 results in a clear benefit in cancer treatment by different mechanisms, including selective killing of homologous recombination-deficient tumor cells, downregulation of tumor-related gene expression, and decrease in the apoptotic threshold in the cotreatment with chemo-and radiotherapy. We summarize in this review the findings and concepts for the role of PARP-1 and poly(ADP-ribosylation) in the regulation of carcinogenesis and some of the preclinical and clinical data available for these agents, together with the challenges facing the clinical development of these agents.

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Authors and Affiliations

  1. Instituto de Parasitología y Biomedicina López Neyra, CSIC, Avda. Conocimiento s/n, ES-18100, Granada, Spain

    Andreína Peralta-Leal, María Isabel Rodríguez & Francisco Javier Oliver

Authors
  1. Andreína Peralta-Leal
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  2. María Isabel Rodríguez
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  3. Francisco Javier Oliver
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Correspondence to Francisco Javier Oliver.

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Supported by an unrestricted educational grant from Pfizer.

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Peralta-Leal, A., Rodríguez, M.I. & Oliver, F.J. Poly(ADP-ribose)polymerase-1 (PARP-1) in carcinogenesis: potential role of PARP inhibitors in cancer treatment. Clin Transl Oncol 10, 318–323 (2008). https://doi.org/10.1007/s12094-008-0207-8

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  • DOI: https://doi.org/10.1007/s12094-008-0207-8

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