Prospects for PARG inhibitors in cancer therapy

Yangchan Hu; Yuxin Meng; Zirui Zhuang; Yuancong Li; Junjun Nan; Ning Xu; Zu Ye; Ji Jing

doi:10.1093/jmcb/mjae050

Prospects for PARG inhibitors in cancer therapy

J Mol Cell Biol. 2024 Dec 12:mjae050. doi: 10.1093/jmcb/mjae050. Online ahead of print.

Authors

Yangchan Hu^{1

2}, Yuxin Meng^{1

2}, Zirui Zhuang^{2

3}, Yuancong Li^{1

2}, Junjun Nan^{1

2}, Ning Xu⁴, Zu Ye^{5

6}, Ji Jing^{2

6}

Affiliations

¹ College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China.
² Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China.
³ School of Molecular Medicine, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences (UCAS), Hangzhou 310024, China.
⁴ Institute of Drug Development & Chemical Biology, College of Pharmaceutical Science, Zhejiang University of Technology, Huzhou 313200, China.
⁵ Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HlM), Chinese Academy of Sciences, Hangzhou 310022, China.
⁶ Zhejiang Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer, Hangzhou 310022, China.

PMID: 39668635
DOI: 10.1093/jmcb/mjae050

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.

Keywords: PARG; PARG inhibitor; cancer therapy.