PARPs and ADP-ribosyl hydrolases in cancer therapy: From drug targets to biomarkers

IF 3 3区生物学 Q2 GENETICS & HEREDITY

DNA Repair Pub Date : 2025-06-24 DOI:10.1016/j.dnarep.2025.103863

Joséphine Groslambert , Kira Schützenhofer , Luca Palazzo , Ivan Ahel

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引用次数: 0

Abstract

The PARP family of enzymes catalyzes ADP-ribosylation, a modification of macromolecules, and plays a crucial role in DNA damage repair. The landmark discovery that cancer cells deficient in homologous recombination repair are highly sensitive to PARP inhibitors has paved the way for the clinical success of multiple PARP inhibitors in the treatment of breast, ovarian, pancreatic, and prostate cancers. This clinical success has spurred interest in targeting additional regulators of ADP-ribosylation, with the ADP-ribosyl hydrolase PARG emerging as a promising therapeutic target. Pre-clinical studies have revealed that PARG inhibitors amplify and exploit replication-associated defects, offering a therapeutic window distinct from that of PARP inhibitors. This review provides an overview of the physiological functions of PARPs and PARG, examines the molecular and cellular effects of their inhibitors, and discusses their clinical applications. Finally, we explore the potential of other ADP-ribosylation regulators as novel cancer biomarkers.

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parp和adp核苷水解酶在癌症治疗中的应用：从药物靶点到生物标志物

PARP家族酶催化adp核糖基化，这是一种大分子修饰，在DNA损伤修复中起着至关重要的作用。具有里程碑意义的发现是，缺乏同源重组修复的癌细胞对PARP抑制剂高度敏感，这为多种PARP抑制剂在治疗乳腺癌、卵巢癌、胰腺癌和前列腺癌方面的临床成功铺平了道路。这一临床成功激发了人们对adp -核糖基化的其他调节因子的兴趣，adp -核糖基水解酶PARG成为一个有希望的治疗靶点。临床前研究表明，PARG抑制剂放大和利用复制相关缺陷，提供了一个不同于PARP抑制剂的治疗窗口。本文综述了PARPs和PARG的生理功能，探讨了它们的抑制剂的分子和细胞作用，并讨论了它们的临床应用。最后，我们探索了其他adp核糖基化调节因子作为新型癌症生物标志物的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

DNA Repair 生物-毒理学

CiteScore

7.60

自引率

5.30%

发文量

审稿时长

59 days

期刊介绍： DNA Repair provides a forum for the comprehensive coverage of DNA repair and cellular responses to DNA damage. The journal publishes original observations on genetic, cellular, biochemical, structural and molecular aspects of DNA repair, mutagenesis, cell cycle regulation, apoptosis and other biological responses in cells exposed to genomic insult, as well as their relationship to human disease. DNA Repair publishes full-length research articles, brief reports on research, and reviews. The journal welcomes articles describing databases, methods and new technologies supporting research on DNA repair and responses to DNA damage. Letters to the Editor, hot topics and classics in DNA repair, historical reflections, book reviews and meeting reports also will be considered for publication.