Deciphering the insights of poly(ADP-ribosylation) in tumor progression

Med Res Rev. 2015 Jul;35(4):678-97. doi: 10.1002/med.21339. Epub 2015 Jan 21.

Abstract

Poly (ADP-ribose) polymerase (PARP) inhibitors are particularly efficient against tumors with defects in the homologous recombination repair pathway. Nonetheless poly(ADP-ribosylation) (PARylation) modulates prometastasic activities and adaptation of tumor to a hostile microenvironment. Modulation of metastasis-promoting traits is possible through the alteration of key transcription factors involved in the regulation of the hypoxic response, the recruitment of new vessels (or angiogenesis), and the stimulation of epithelial to mesenchymal transition (EMT). In this review, we summarized some of the findings that focalize on PARP-1's action on tumor aggressiveness, suggesting new therapeutic opportunities against an assembly of tumors not necessarily bearing DNA repair defects. Metastasis accounts for the vast majority of mortality derived from solid cancer. PARP-1 is an active player in tumor adaptation to metastasis and PARP inhibitors, recognized as promising therapeutic agents against homologous recombination deficient tumors, has novel properties responsible for the antimetastatic actions in different tumor settings.

Keywords: EMT; PARP; angiogenesis; hypoxia; metastasis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Hypoxia
  • Disease Progression*
  • Epithelial-Mesenchymal Transition
  • Humans
  • Neoplasms / blood supply
  • Neoplasms / metabolism*
  • Neoplasms / pathology*
  • Poly Adenosine Diphosphate Ribose / metabolism*
  • Poly(ADP-ribose) Polymerases / metabolism

Substances

  • Poly Adenosine Diphosphate Ribose
  • Poly(ADP-ribose) Polymerases