Deciphering the Insights of Poly(ADP-Ribosylation) in Tumor Progression

作者:Isabel Rodriguez Maria; Majuelos Melguizo Jara; Marti Martin Consuegra Juan Manuel; Ruiz de Almodovar Mariano; Lopez Rivas Abelardo; Javier Oliver Francisco
来源:Medicinal Research Reviews, 2015, 35(4): 678-697.
DOI:10.1002/med.21339

摘要

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.

  • 出版日期2015-7