Poly(ADP-ribose) polymerase inhibitor therapeutic effect: are we just scratching the surface?

Abstract

Poly(ADP-ribose) polymerase (PARP) research has come a long way since the discovery of the enzyme 50 years ago. Since the development of first-generation PARP inhibitors (PARPi), numerous clinical trials have been performed to validate their safety and efficacy, bringing us to the stage at which a PARPi is now a valuable treatment option for patients with ovarian cancer. Nevertheless, the exact molecular mechanism of the PARPi anti-tumor effect is under debate and PARPi are not specific for a single enzyme. Moreover, the anti-inflammatory activity of PARPi in preclinical experiments has not been explored much so far. Thus, further basic and preclinical research is needed to advance the use of PARPi in the treatment of tumors and potentially other inflammation-associated diseases.

Keywords: ADP-ribosyltransferases diphtheria toxin-like; poly(ADP-ribose) polymerase inhibitors; poly-ADP-ribose; synthetic lethality; tumor.