Clinical and Translational Oncology

, Volume 10, Issue 6, pp 318–323

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

  • Andreína Peralta-Leal
  • María Isabel Rodríguez
  • Francisco Javier Oliver
Educational Series

DOI: 10.1007/s12094-008-0207-8

Cite this article as:
Peralta-Leal, A., Rodríguez, M.I. & Oliver, F.J. Clin Transl Oncol (2008) 10: 318. doi:10.1007/s12094-008-0207-8
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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.

Keywords

PARP-1CarcinogenesisDNA repairAntineoplasic therapy

Copyright information

© Feseo 2008

Authors and Affiliations

  • Andreína Peralta-Leal
    • 1
  • María Isabel Rodríguez
    • 1
  • Francisco Javier Oliver
    • 1
  1. 1.Instituto de Parasitología y Biomedicina López NeyraCSICGranadaSpain