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DNA methyltransferase inhibitors combination therapy for the treatment of solid tumor: mechanism and clinical application
Clinical Epigenetics ( IF 4.8 ) Pub Date : 2021-08-27 , DOI: 10.1186/s13148-021-01154-x
Chunhong Hu 1, 2 , Xiaohan Liu 1 , Yue Zeng 1 , Junqi Liu 1 , Fang Wu 1, 2, 3, 4
Affiliation  

DNA methylation, an epigenetic modification, regulates gene transcription and maintains genome stability. DNA methyltransferase (DNMT) inhibitors can activate silenced genes at low doses and cause cytotoxicity at high doses. The ability of DNMT inhibitors to reverse epimutations is the basis of their use in novel strategies for cancer therapy. In this review, we examined the literature on DNA methyltransferase inhibitors. We summarized the mechanisms underlying combination therapy using DNMT inhibitors and clinical trials based on combining hypomethylation agents with other chemotherapeutic drugs. We also discussed the efficacy of such compounds as antitumor agents, the need to optimize treatment schedules and the regimens for maximal biologic effectiveness. Notably, the combination of DNMT inhibitors and chemotherapy and/or immune checkpoint inhibitors may provide helpful insights into the development of efficient therapeutic approaches.

中文翻译:

DNA甲基转移酶抑制剂联合治疗实体瘤:机制及临床应用

DNA甲基化是一种表观遗传修饰,可调节基因转录并维持基因组稳定性。DNA甲基转移酶(DNMT)抑制剂可以在低剂量时激活沉默的基因,在高剂量时引起细胞毒性。DNMT 抑制剂逆转表观突变的能力是它们用于癌症治疗新策略的基础。在这篇综述中,我们检查了有关 DNA 甲基转移酶抑制剂的文献。我们总结了使用 DNMT 抑制剂进行联合治疗的机制,以及基于低甲基化药物与其他化疗药物联合的临床试验。我们还讨论了此类化合物作为抗肿瘤剂的功效、优化治疗方案的必要性以及最大生物有效性的方案。尤其,
更新日期:2021-08-27
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