靶向脱脂血酶在癌症治疗中的应用

IF 3 3区生物学 Q2 GENETICS & HEREDITY

DNA Repair Pub Date : 2025-03-05 DOI:10.1016/j.dnarep.2025.103824

Peng Li , Duo Wu , Xiaochun Yu

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引用次数: 0

摘要

聚（adp -核糖）核糖化（PARylation）是由聚（adp -核糖）聚合酶（PARPs）介导的可逆翻译后修饰，在DNA复制和DNA损伤修复中起着至关重要的作用。由于干扰PARP修饰可诱导具有同源重组缺陷的肿瘤细胞的选择性细胞毒性，PARP抑制剂（PARPi）在治疗brca突变型癌症患者中具有重要的临床作用。同样，脱欧化对于优化DNA损伤反应和基因组稳定性也是必不可少的。这一过程是由一组磷脂酰化酶介导的，如聚（adp -核糖）糖水解酶（PARG）。目前，一些新的PARG抑制剂已经开发出来，并在临床前和临床研究中进行了检测，显示出不同于PARP抑制剂的有希望的抗癌活性。本文综述了PARG在基因组稳定性中的作用以及PARG抑制剂在癌症治疗中的潜力。

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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Targeting dePARylation in cancer therapy

Poly(ADP-ribosyl)ation (PARylation), a reversible post-translational modification mediated by poly(ADP-ribose) polymerases (PARPs), plays crucial roles in DNA replication and DNA damage repair. Since interfering PARylation induces selective cytotoxicity in tumor cells with homologous recombination defects, PARP inhibitors (PARPi) have significant clinical impacts in treating BRCA-mutant cancer patients. Likewise, dePARylation is also essential for optimal DNA damage response and genomic stability. This process is mediated by a group of dePARylation enzymes, such as poly(ADP-ribose) glycohydrolase (PARG). Currently, several novel PARG inhibitors have been developed and examined in preclinical and clinical studies, demonstrating promising anti-cancer activity distinct from PARP inhibitors. This review discusses the role of dePARylation in genome stability and the potential of PARG inhibitors in cancer therapy.

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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.