Prospects for PARG inhibitors in cancer therapy

Abstract Poly(ADP-ribose) glycosylhydrolase (PARG) is an enzyme involved in hydrolyzing the ribose–ribose bonds present in poly(ADP-ribose) (PAR), which are primarily found in the nucleus. Along with poly(ADP-ribose) polymerase (PARP), PARG regulates the level of PAR in cells, playing a crucial role in DNA maintenance and repair processes. Recent studies have revealed elevated levels of PARG in various cancers, such as breast, liver, prostate, and esophageal cancers, indicating a link to unfavorable cancer outcomes. PARG is a significant molecular target for treating PAR-related cancers. This review provides a comprehensive overview of the physiological role of PARG and the development of its inhibitors, highlighting its potential as an innovative target for cancer treatment.