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Therapeutic Effects of HDAC Inhibitors

HDAC inhibitors to treat cancer
As previously mentioned, two HDAC inhibitors, vorinostat and depsipetide, have recently been approved by the FDA in 2006 and 2009, respectively. This marks the official recognition of HDAC inhibitors as emerging therapeutic agents in treating he-matologic malignancies, including cutaneous T-cell lymphoma (CTCL). Although the specific MOA (mechanisms of action) of HDAC inhibitors are still not crystalized, they have been clinically validated in cancer treatment as either single agents or in combination with conventional chemotherapies or simply as targeted drugs. Several clinical trials are currently on-going.

HDAC inhibitors are well tolerated and clinically effective against hematologic cancers, but admittedly, they have poor anti-cancer performance against solid tumors when used as a mono-therapy.

HDAC inhibitors to treat inflammatory diseases
In addition to its anticancer effects, HDAC inhibitors have a newly delineated role in modulating the activity of the immune system, offering new lines of therapeutic intervention for rheumatoid arthritis or lupus erythematosus. Yet the MOA of HDAC inhibitors in this regard is still uncertain. Considering the rising importance of immunotherapy in cancer treatment, these anti-inflammatory effects will hopefully lead us to appreciate the complex anti-tumor effects of HDAC inhibitors.

While documentation of the anti-inflammatory nature of many HDAC inhibitors could be traced back quite earlier, this effect varies with dose, and the optimum dose of each HDAC inhibitor is not the same. Inhibitors TSA and SAHA have shown promise in future treatment for type 1 diabetes, a metabolic disease which has a substantial inflammatory component.

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