靶向治疗染色质重塑因子ARID1A突变肿瘤的分子机理  

Molecular Mechanism of Targeted Therapy of Chromatin Remodeling Factor ARID1A Mutant Tumors

作　　者：杨淑娴 陈佳钰 孙序序 王英 YANG Shuxian;CHEN Jiayu;SUN Xuxu;WANG Ying(Department of Biochemistry and Molecular Cell Biology,State Key Laboratory of Oncogenes and Related Genes,Shanghai Key Laboratory for Tumor Microenvironment and Inflammation,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China)

机构地区：[1]上海交通大学医学院生物化学与分子细胞生物学系,上海市肿瘤微环境与炎症重点实验室,癌基因及相关基因国家重点实验室,上海200025

出　　处：《中国细胞生物学学报》2022年第7期1407-1415,共9页Chinese Journal of Cell Biology

基　　金：国家自然科学基金(批准号:31970587);上海交通大学医学院“大学生创新训练计划”(第十四期项目)(批准号:1420Y022);2021年上海市级“大学生创新训练计划”(批准号:S202110248112)资助的课题。

摘　　要：染色质重塑因子ARID1A(the AT-rich interaction domain 1A)基因是肿瘤中突变率最高的基因之一,ARID1A突变通常导致其蛋白质表达和功能缺失,ARID1A突变的肿瘤细胞和小鼠模型均证明ARID1A突变可促进肿瘤发生发展,提示ARID1A突变在肿瘤演化中的恶性作用。挖掘靶向ARID1A突变肿瘤细胞的治疗方式和药物靶标有助于未来靶向ARID1A突变肿瘤的临床药物研发,且具有临床应用意义。该文总结了针对ARID1A突变肿瘤细胞的合成致死(synthetic lethality)方法和ARID1A突变肿瘤免疫治疗策略的分子机理和最新研究进展,旨在为未来探索ARID1A突变肿瘤的临床治疗方法提供参考。Chromatin remodeling factor ARID1A(the AT-rich interaction domain 1A)is one of the genes with the highest mutation rate in many types of tumors.ARID1A mutations usually lead to the loss of protein expression and function.Both tumor cells and mouse models with ARID1A mutation proved that ARID1A mutation promoted tumor development,suggesting the malignant role of ARID1A mutation in tumor evolution.The exploration of therapeutic methods and drug targets for ARID1A mutant tumor cells will contribute to the future clinical drug development targeting ARID1A mutant tumors,which has clinical application significance.This paper summarized the latest molecular mechanism and research progress of the synthetic lethal methods and immunotherapy strategies for ARID1A mutant tumors,providing reference for future clinical treatment of ARID1A mutant tumor.

关 键 词：ARID1A 抑癌基因 基因突变 免疫治疗 合成致死 

分 类 号：R730.5[医药卫生—肿瘤]