癌症中的DNA甲基化及其靶向治疗研究现状

Research status of DNA methylation and targeted therapy in cancer

摘要

DNA甲基化在调控基因表达模式、保持基因组结构稳定以及维持染色体构象方面发挥着关键作用。其异常状态与细胞癌变、肿瘤的发生发展密切相关。抑癌基因启动子区的高甲基化引起的表达抑制已成为癌症的显著特征。目前, 针对肿瘤细胞中DNA甲基转移酶及去甲基化酶的靶向治疗策略日益增多。本综述系统回顾了癌症中DNA异常甲基化的发生位点、调节机制以及靶向治疗方案, 旨在总结该领域的最新研究成果, 并探讨DNA甲基化靶向治疗在临床应用中的现状与前景。

Abstract

DNA methylation is a crucial mechanism in regulating gene expression patterns and maintaining genomic structural stability and chromosome conformation. Aberrant DNA methylation is closely related to the occurrence, development and carcinogenesis of tumors. Expression silencing induced by hypermethylation in the promoter region of tumor suppressor genes has become a prominent feature of cancer. Novel therapeutic strategies targeting DNA methyltransferase and demethylase in tumor cells have been developed. In this review, the occurrence sites, regulatory mechanisms, and targeted therapeutic approaches of aberrant DNA methylation in cancer were reviewed, aiming to recapitulate the latest research progress on DNA methylation in cancer, and to explore the current status and prospects of DNA methylation-targeted therapy in clinical applications.

关键词

DNA甲基化 / 肿瘤 / DNA甲基转移酶 / 脱甲基酶 / 分子靶向治疗 / 抗肿瘤药 / 基因表达调控 / 表观遗传学

Key words

DNA methylation / neoplasms / DNA methyltransferase / demethylases / molecular targeted therapy / antineoplastic agents / gene expression regulation / epigenetics

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基金资助

国家自然科学基金(81802800)

陕西省重点研发计划项目(2021SF058)

空军军医大学“临床医学+X”研究中心科研课题(LHJJ24JH28)

空军军医大学基础医学院教学课题(2025-JCJXKT-YB-13)