The Role of the DNA Methyltransferase Family and the Therapeutic Potential of DNMT Inhibitors in Tumor Treatment.

Abstract

Members of the DNA methyltransferase (DNMT) family have been recognized as major epigenetic regulators of altered gene expression during tumor development. They establish and maintain DNA methylation of the CpG island of promoter and non-CpG region of the genome. The abnormal methylation status of tumor suppressor genes (TSGs) has been associated with tumorigenesis, leading to genomic instability, improper gene silence, and immune evasion. DNMT1 helps preserve methylation patterns during DNA replication, whereas the DNMT3 family is responsible for de novo methylation, creating new methylation patterns. Altered DNA methylation significantly supports tumor growth by changing gene expression patterns. FDA-approved DNMT inhibitors reverse hypermethylation-induced gene repression and improve therapeutic outcomes for cancer. Recent studies indicate that combining DNMT inhibitors with chemotherapies and immunotherapies can have synergistic effects, especially in aggressive metastatic tumors. Improving the treatment schedules, increasing isoform specificity, reducing toxicity, and utilizing genome-wide analyses of CRISPR-based editing to create personalized epigenetic therapies tailored to individual patient needs are promising strategies for enhancing therapeutic outcomes. This review discusses the interaction between DNMT regulators and DNMT1, its binding partners, the connection between DNA methylation and tumors, how these processes contribute to tumor development, and DNMT inhibitors' advancements and pharmacological properties.