共济失调毛细血管扩张突变基因在胃癌中的研究现状

Research status of ataxia-telangiectasia mutated gene in gastric cancer

共济失调毛细血管扩张突变(ATM)基因是共济失调毛细血管扩张症唯一的致病基因。由于ATM基因突变使其编码的ATM蛋白表达缺失,从而丧失对下游基因的调控作用,使得受损伤DNA的合成受到抑制,阻碍DNA的修复过程,进而导致染色体的断裂和基因组的不稳定,最终引起细胞凋亡率和肿瘤发生率的升高。ATM基因突变与胃癌的发生、侵袭及转移相关。ATM突变或缺失的这部分胃癌患者对放疗、铂类化疗的敏感性增加,并且在免疫抑制药应用中观察到明显的临床获益。靶向ATM突变抑制药的研发在与放化疗及其他小分子靶点药物治疗的联合应用中表现出更大的生存获益。本文结合近期对ATM在胃癌中的研究进展进行综述,旨在为胃癌的精准化治疗提供潜在的新靶点。

The ataxia-telangiectasia mutation(ATM)gene is the only causative gene for the ataxia telangiectasia.Due to the mutation of the ATM gene,the expression of the encoded ATM protein is lost,thereby losing the regulation of downstream genes,inhibiting the synthesis of damaged DNA,hindering the DNA repair process,and then leading to chromosome breakage and genome instability,and finally resulting in increased apoptosis rate and tumor incidence.ATM gene mutation is associated with the occurrence,invasion and metastasis of gastric cancer.This part of gastric cancer with ATM mutations or deletions has increased sensitivity to radiotherapy and platinum-based chemotherapy,and significant clinical benefit has been observed in the application of immunosuppressive agents.The development of targeted ATM mutation inhibitors has shown greater survival benefit in combination with chemoradiotherapy and other small-molecule-targeted drug therapies.This article reviews the recent research progress of ATM in gastric cancer,aiming to provide potential new targets for the precise treatment of gastric cancer.