Advances in the research of ATM/ATR inhibitor-mediated synthetic lethality in prostate cancer
10.3781/j.issn.1000-7431.2025.2412-0758
- VernacularTitle:基于ATM/ATR抑制剂合成致死策略治疗前列腺癌的研究进展
- Author:
Chengqi JIN
1
;
Yajuan HAO
;
Bin YANG
Author Information
1. 安徽理工大学医学院,淮南 232001;同济大学医学院泌尿肿瘤研究所,上海 200072
- Publication Type:Journal Article
- Keywords:
Prostate cancer;
Ataxia telangiectasia-mutated gene;
Ataxia telangiectasia and Rad3-related protein inhibitor;
Synthetic lethality;
Homologous recombination repair
- From:
Tumor
2025;45(2):159-169
- CountryChina
- Language:Chinese
-
Abstract:
With the progression of global population aging,the incidence and mortality of prostate cancer have been increasing year by year,drawing widespread attention from all sectors of society.Based on the synthetic lethality strategy,the U.S.Food and Drug Administration(FDA)has successively approved multiple poly ADP-ribose polymerase(PARP)inhibitors for the treatment of metastatic castration-resistant prostate cancer(mCRPC)in recent years.This advancement has greatly stimulated the interest of researchers in novel synthetic lethal combination:the ataxia telangiectasia-mutated(ATM)gene and the ataxia telangiectasia and Rad3-related protein(ATR).In the DNA damage repair pathway,the ATM kinase primarily participates in the repair of DNA double-strand breaks,while ATR plays a crucial role in the repair of DNA single-strand breaks and exerts a positive regulatory function.ATR inhibitors are considered one of the most promising synthetic lethal targeted agents following PARP inhibitors,offering potential as a novel therapeutic option for patients with ATM gene mutations.However,current clinical research data on ATR inhibitors in the treatment of prostate cancer remain insufficient.Therefore,a deeper understanding of the synthetic lethality mechanism involving the ATM/ATR kinase combination is of crucial importance for advancing precision therapy of prostate cancer.
