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实体瘤患者的表观遗传疗法:聚焦于脱氧核糖核酸甲基转移酶抑制剂和组蛋白脱乙酰酶抑制剂的单药治疗。

Epigenetic therapies in patients with solid tumors: Focus on monotherapy with deoxyribonucleic acid methyltransferase inhibitors and histone deacetylase inhibitors.

作者信息

Katarzyna Rygiel, Lucyna Bulas

机构信息

Department of Family Practice, Medical University of Silesia (SUM), Katowice-Zabrze, Zabrze, Poland.

Department of Pharmacy, Medical University of Silesia (SUM), Katowice, Poland.

出版信息

J Cancer Res Ther. 2019 Jul-Sep;15(5):961-970. doi: 10.4103/jcrt.JCRT_403_17.

DOI:10.4103/jcrt.JCRT_403_17
PMID:31603095
Abstract

Epigenomics is the study of the gene expression changes due to epigenetic processes and not due to the deoxyribonucleic acid (DNA) base sequence alterations. The key mechanisms of epigenetic regulation include DNA methylation, histone modifications, and noncoding RNAs. Epigenetic alterations in cancer are predominantly linked with hypermethylation of promoters of the tumor suppressor genes, global DNA hypomethylation, and increased expression of histone deacetylases (HDAC). There is a growing need to investigate epigenetic patterns and to provide safe and effective, innovative therapeutic strategies for oncology patients, who did not improve on traditional anticancer regimens. The epi-drugs (e.g., DNA methyltransferase inhibitors, e.g., azacitidine and decitabine and HDAC inhibitors, e.g., vorinostat and romidepsin) have been approved for the clinical use. In this paper, we provide a brief overview of the mechanisms of action and targets for novel epi-drugs, focusing on their potential clinical applications in patients with solid tumors, resistant to standard oncology treatments.

摘要

表观基因组学是研究由表观遗传过程而非脱氧核糖核酸(DNA)碱基序列改变引起的基因表达变化。表观遗传调控的关键机制包括DNA甲基化、组蛋白修饰和非编码RNA。癌症中的表观遗传改变主要与肿瘤抑制基因启动子的高甲基化、全基因组DNA低甲基化以及组蛋白去乙酰化酶(HDAC)表达增加有关。对于那些在传统抗癌方案中未取得改善的肿瘤患者,越来越需要研究表观遗传模式并提供安全有效的创新治疗策略。表观遗传药物(如DNA甲基转移酶抑制剂,如阿扎胞苷和地西他滨,以及HDAC抑制剂,如伏立诺他和罗米地辛)已被批准用于临床。在本文中,我们简要概述了新型表观遗传药物的作用机制和靶点,重点关注它们在对标准肿瘤治疗耐药的实体瘤患者中的潜在临床应用。

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