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Abstract
Chromatin modeling in DNA is fundamental to gene expression, DNA repair and replication. Methylation of promoter regions of tumor-suppressor genes and histone deacetylation leads to gene silencing and transcriptionally repressive chromatin. Histone deacetylase inhibitors and hypomethylating agents allow upregulation of proapoptotic genes and downregulation of antiapoptotic genes, and show significant single-agent anticancer activity, predominantly in cutaneous T-cell lymphoma and myelodysplasia, respectively. Combinations of these drugs are being employed in clinical trials to target multiple biological pathways, with the hope of synergistic pharmacodynamics. Preclinical studies of combinations of these agents with chemotherapy, monoclonal antibodies and small-molecule inhibitors are ongoing and demonstrate synergy in multiple hematological cancers, raising the prospect of future treatment for these diseases having a multitargeted approach.
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
Notes
TRAIL: Tumor necrosis factor-related apoptosis-inducing ligand.