Recent progress in DNA methyltransferase inhibitors as anticancer agents

Zhixiong Zhang; Guan Wang; Yuyan Li; Dongsheng Lei; Jin Xiang; Liang Ouyang; Yanyan Wang; Jinliang Yang

doi:10.3389/fphar.2022.1072651

Recent progress in DNA methyltransferase inhibitors as anticancer agents

Front Pharmacol. 2022 Dec 16:13:1072651. doi: 10.3389/fphar.2022.1072651. eCollection 2022.

Authors

Zhixiong Zhang^{1

2}, Guan Wang¹, Yuyan Li^{1

2}, Dongsheng Lei³, Jin Xiang¹, Liang Ouyang^{1

4}, Yanyan Wang^{1

4}, Jinliang Yang¹

Affiliations

¹ State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, Innovation Center of Nursing Research, West China Hospital, and Collaborative Innovation Center of Biotherapy, Sichuan University, Chengdu, China.
² Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.
³ School of Physical Science and Technology, Electron Microscopy Center of Lanzhou University, Lanzhou University, Lanzhou, China.
⁴ Science and Technology Department, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.

Abstract

DNA methylation mediated by DNA methyltransferase is an important epigenetic process that regulates gene expression in mammals, which plays a key role in silencing certain genes, such as tumor suppressor genes, in cancer, and it has become a promising therapeutic target for cancer treatment. Similar to other epigenetic targets, DNA methyltransferase can also be modulated by chemical agents. Four agents have already been approved to treat hematological cancers. In order to promote the development of a DNA methyltransferase inhibitor as an anti-tumor agent, in the current review, we discuss the relationship between DNA methylation and tumor, the anti-tumor mechanism, the research progress and pharmacological properties of DNA methyltransferase inhibitors, and the future research trend of DNA methyltransferase inhibitors.

Keywords: DNA methylation; DNA methyltransferase; DNA methyltransferase inhibitor; epigenetic; tumor immunotherapy.

Publication types

Review

Grants and funding

This work was supported by grants from the Technological Special Project for “Significant New Drugs Development” (Grant Nos. 2018ZX09201018-021 and 2018ZX09201018-020), the National Natural Science Foundation of China (Grant No. 82073318), the National Major Scientific and Sichuan Science and Technology Program (Grant No. 2019YFS0003), the National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University (Grant No. Z20201004), the Post-Doctor Research Project, West China Hospital, Sichuan University (2020HXBH020), the Science and Technology Project of the Health Planning Committee of Sichuan (20PJ022), and the Ministry of Science and Technology Project of the People’s Republic of China (2018YFC2001802-1).