DNA (cytosine-5-)-methyltransferase 1, DNA (cytosine-5-)-methyltransferase 3 beta, and histone deacetylases (DNMT1/DNMT3B/HDACs)

DNA (cytosine-5-)-methyltransferase 1 (DNMT1), DNA (cytosine-5-)-methyltransferase 3 beta (DNMT3B), and histone deacetylases (HDACs) are a group of epigenetic enzymes that cooperatively regulate gene expression by modifying DNA and chromatin structure [1, 17]. DNMT1 is primarily responsible for maintaining DNA methylation patterns during replication, while DNMT3B facilitates de novo methylation; HDACs remove acetyl groups from histones, leading to a condensed, transcriptionally inactive chromatin state [9, 19, 23]. In many cancers, these enzymes are overexpressed or dysregulated, resulting in the silencing of tumor suppressor genes and the promotion of cancer stem cell survival [1, 11]. Therapeutic strategies targeting this axis involve combination treatments or dual-action inhibitors designed to reactivate silenced genes and induce a 'viral mimicry' response, where the reactivation of endogenous retroviruses triggers an immune-mediated antitumour effect [3, 5, 6]. This multi-target approach has shown significant potential in overcoming drug resistance and enhancing the efficacy of immune checkpoint blockades [5, 13, 20].

Other names

DNMT1DNMT3BHDACsDNA (cytosine-5-)-methyltransferase 1DNA (cytosine-5-)-methyltransferase 3 betaHistone deacetylase familyDNA methyltransferase 1DNA methyltransferase 3 beta

Simultaneous inhibition of DNA methyltransferases and histone deacetylases to reverse epigenetic silencing of tumor suppressor genes, induce viral mimicry through endogenous retrovirus reactivation, and enhance antitumour immunity [3, 5, 6, 15].