共济失调毛细血管扩张突变基因在膀胱癌治疗中的研究现状  

The current research status of ataxia telangiectasia mutated gene in the treatment of bladder cancer

作　　者：范龙梅 唐佳佳 黄天渝 廖远键 左明顺 张能 张江容 FAN Longmei;TANG Jiajia;HUANG Tianyu;LIAO Yuanjian;ZHANG Neng;ZHANG Jiangrong(Department of Urology,Zunyi Medical University,Zunyi 5630006,Guizhou Province,China;School of Nursing,Zunyi Medical University,Zunyi 5630006,Guizhou Province,China)

机构地区：[1]遵义医科大学附属医院泌尿外科,贵州遵义5630006 [2]遵义医科大学护理学院,贵州遵义5630006

出　　处：《肿瘤》2024年第10期1044-1050,共7页Tumor

基　　金：国家自然科学基金资助项目(81860524);遵义市科技计划课题项目[遵市科合HZ字(2022)308]

摘　　要：共济失调毛细血管扩张突变(ataxia telangiectasia mutated,ATM)基因是一种重要的抑癌基因,也是调控DNA双链损伤修复的关键效应基因,其在维持基因组稳定性、促进细胞周期阻滞以及调控细胞凋亡的过程中发挥着不可替代的作用。当ATM基因发生突变后,其无法有效诱导下游靶标的磷酸化过程,进而导致DNA修复机制受损,引发基因组不稳定性和染色体结构异常,最终促使肿瘤细胞异常增殖。二代测序(next generation seqence,NGS)数据的分析结果表明,膀胱癌细胞中ATM基因的突变率相对较高。已有相关研究证实ATM基因会通过核转录因子-κB(nuclear transcriptionfactor-κB,NF-κB)以及干扰素γ(interferon-γ,IFNγ)等信号通路调控膀胱癌细胞的增殖、浸润和转移。而突变的ATM基因能够增强患者对放化疗的敏感性,并提升免疫治疗的疗效,因此携带此类突变的患者总体预后相对较好。这一发现使得ATM基因有望成为膀胱癌治疗的潜在靶点,并作为预测患者预后的生物标志物。鉴于此,本文将从ATM基因的结构特征及其抑癌与促癌功能,ATM基因在膀胱癌发生与发展过程中的作用机制,以及ATM基因对膀胱癌患者治疗和预后的影响3个方面,对ATM基因在膀胱癌中的研究进行全面综述,并对其未来研究方向进行展望,以期为膀胱癌的药物治疗提供新的靶点,为膀胱癌患者的治疗带来新的希望。The ataxia telangiectasia mutated(ATM)gene is an important tumor suppressor gene and a key effector gene in regulating the repair of double-strand DNA breaks.It plays an indispensable role in maintaining genetic stability,facilitating cell cycle arrest,and modulating cell apoptosis.When the ATM gene mutates,it fails to effectively induce the phosphorylation of downstream targets,leading to impaired DNA repair mechanisms,genetic instability,and chromosomal structural abnormalities,ultimately promoting abnormal proliferation of tumor cells.Analysis of next-generation sequencing(NGS)datas reveals a relatively high mutation rate of the ATM gene in bladder cancer cells.Relevant studies have shown that ATM gene regulates the proliferation,invasion,and metastasis of bladder cancer cells through the signaling pathways such as nuclear transcription factor-κB(NF-κB)and Interferon-γ(IFNγ).Mutanted ATM gene can enhance patients'sensitivity to radiotherapy and chemotherapy,and boost the efficacy of immunotherapy,resulting in a generally better prognosis for patients with ATM gene mutation.This finding marks ATM gene as a potential therapeutic target and predictive prognosis biomarker for bladder cancer patients.Therefore,this article will comprehensively review the research on the ATM gene in bladder cancer from 3 aspects:the structural characteristics of the ATM gene and its tumor-suppressing and tumor-promoting functions,the mechanism of action of the ATM gene in the occurrence and development of bladder cancer,and the impact of the ATM gene on the treatment and prognosis of bladder cancer patients.Additionally,the future research directions of the ATM gene was prospected,with the aim of providing new targets for the drug treatment of bladder cancer,and bringing new hope for the treatment of bladder cancer patients.

关 键 词：膀胱癌 共济失调毛细血管扩张突变 DNA损伤 靶向治疗 

分 类 号：R737.14[医药卫生—肿瘤]