PARP molecular functions and applications of PARP inhibitors in cancer treatment

Abstract

Poly(ADP-ribosyl)ation (PARylation), a type of post-translational modification catalyzed by poly(ADP-ribose) polymerase (PARP), is implicated in numerous biological processes including DNA repair, chromatin remodeling, programmed cell death, RNA regulation, and PAR-dependent ubiquitination. The advent of PARP inhibitors represents a new synthetic lethality paradigm for killing tumors bearing BRCA mutations in which tumor-specific defects are exploited to create a vulnerability that causes tumor cell death. To date, four PARP inhibitors have been approved by the US Food and Drug Administration for treatment of several types of cancer. In this review, we summarize the current knowledge of the molecular functions of PARP1 and highlight the recent advances in the use of PARP inhibitors in cancer treatment and the problem of drug resistance.

Funding

National Natural Science Foundation of China(T2225006); Natural Science Foundation of Beijing Municipality(Z220011)