Poly(ADP-ribose) Polyremase-1 (PARP-1) Inhibition: A Promising Therapeutic Strategy for ETS-Expressing Tumours

Int J Mol Sci. 2023 Aug 30;24(17):13454. doi: 10.3390/ijms241713454.

Abstract

ETS transcription factors are a highly conserved family of proteins involved in the progression of many cancers, such as breast and prostate carcinomas, Ewing's sarcoma, and leukaemias. This significant involvement can be explained by their roles at all stages of carcinogenesis progression. Generally, their expression in tumours is associated with a poor prognosis and an aggressive phenotype. Until now, no efficient therapeutic strategy had emerged to specifically target ETS-expressing tumours. Nevertheless, there is evidence that pharmacological inhibition of poly(ADP-ribose) polymerase-1 (PARP-1), a key DNA repair enzyme, specifically sensitises ETS-expressing cancer cells to DNA damage and limits tumour progression by leading some of the cancer cells to death. These effects result from a strong interplay between ETS transcription factors and the PARP-1 enzyme. This review summarises the existing knowledge of this molecular interaction and discusses the promising therapeutic applications.

Keywords: DNA damage; ETS transcription factors; PARP-1; cancer therapy; pharmacological inhibition.

Publication types

  • Review

MeSH terms

  • Humans
  • Leukemia*
  • Poly Adenosine Diphosphate Ribose
  • Poly(ADP-ribose) Polymerase Inhibitors / pharmacology
  • Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use
  • Prostatic Neoplasms*
  • Sarcoma, Ewing*

Substances

  • Poly Adenosine Diphosphate Ribose
  • Poly(ADP-ribose) Polymerase Inhibitors

Grants and funding

This research was funded by the Centre National de la Recherche Scientifique (CNRS) and by grants from la Ligue contre le Cancer, Comité du Pas-de-Calais.