HDAC Inhibitors induce tumor cell-selective pro-apoptotic transcriptional responses.

The identification of recurrent somatic mutations in genes encoding epigenetic enzymes, coupled with biochemical studies demonstrating aberrant recruitment of epigenetic enzymes such as histone deacetylases (HDACs) and histone methyltransferases (HMTs) to promoter regions through association with oncogenic fusion proteins such as PML-RAR and AML1-ETO has provided a strong rationale for the development compounds that target the epigenome for the treatment of cancer. HDAC inhibitors (HDACi) are potent inducers of tumor cell apoptosis but it remains unclear why tumor cells are selectively sensitive to HDACi-induced cell death.

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Bolden JE, Shi W, Jankowski K, Kan CY, Cluse L, Martin BP, MacKenzie KL, Smyth GK, Johnstone RW