2. Academic Validation
  3. DNA methyltransferase inhibitors combination therapy for the treatment of solid tumor: mechanism and clinical application

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

  • Clin Epigenetics. 2021 Aug 27;13(1):166. doi: 10.1186/s13148-021-01154-x.
Chunhong Hu # 1 2,  Xiaohan Liu # 1,  Yue Zeng 1,  Junqi Liu 1,  Fang Wu 3 4 5 6
Affiliations

Affiliations

  • 1 Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China.
  • 2 Hunan Cancer Mega-Data Intelligent Application and Engineering Research Centre, Changsha, 410011, Hunan, China.
  • 3 Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China. [email protected].
  • 4 Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China. [email protected].
  • 5 Hunan Key Laboratory of Early Diagnosis and Precision Therapy in Lung Cancer, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China. [email protected].
  • 6 Hunan Cancer Mega-Data Intelligent Application and Engineering Research Centre, Changsha, 410011, Hunan, China. [email protected].
  • # Contributed equally.
PMID: 34452630 DOI: 10.1186/s13148-021-01154-x
Abstract

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.

Figures