Journal article

Epigenetic targets in hematological malignancies: Combination therapies with HDACis and demethylating agents

Mark Bishton, Melita Kenealy, Ricky Johnstone, Walid Rasheed, H Miles Prince

Expert Review of Anticancer Therapy | TAYLOR & FRANCIS LTD | Published : 2007


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 combinati..

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