Histone Deacetylase Inhibitors

Histone deacytylase (HDAC) inhibitors are a new class of chemotherapeutic reagents that cause growth arrest and apoptosis of neoplastic cells. In a recent study, depsipep-tide, a new member of the HDAC inhibitors, induced apoptosis in myeloma cell lines in a time- and dose-dependent fashion, and in primary patient myeloma cells.73 Another HDAC inhibitor, suberoylanilide hydroxamic acid (SAHA), potently induced apoptosis of human MM cells.74 SAHA treatment has been shown to suppress the activity of the proteasome and expression of its subunits, thereby enhancing MM cell sensitivity to proteasome inhibition by bortezomib (PS-341).74 SAHA also enhances the anti-MM activity of other proapop-totic agents, including dexamethasone, cytotoxic chemotherapy, and thalidomide analogs.74 This agent has shown encouraging results in a phase I trial.75

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