Gene

Gene expression

DNA methylation

Azacitidine

Combination therapy

DNA methyltransferase

Epigenetic therapy

Methylation

Epigenetics

Cancer research

Genetics

Biology

Methyltransferase

Pharmacology

Clinical Epigenetics

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.

DNA methyltransferase inhibitors combination therapy for the treatment of solid tumor: mechanism and clinical application