HDAC inhibitors, HDI) are a class of compounds that block the activity of histone deacetylase (HDAC), a crucial part of the gene expression cycle within a cell. HDI’s have a long history of use in psychiatry and neurology as mood stabilizers and anti-epileptics. Over the last several years, numerous HDI’s have been found to inhibit cellular proliferation and cause apoptosis of tumor cells. However, the precise mechanisms by which HDI’s arrest tumor growth are still under investigation, and currently just one HDI has been approved for treatment of cancer.
A research team led by Lia Gore and Deb DeRyckere at the University of Colorado has demonstrated a synergistic cell kill effect when a class I-specific HDI is used in combination with another, non-class I-specific HDI. Dr. Gore’s team has shown that class I-specific HDI’s induce cell cycle arrest at the GI stage, whereas other HDI’s act at later stages from G2 thru S. The team has hypothesized that the mechanism of synergy is due to complementary G1 + G2 --> S arrest.
This method for combining a class I-specific HDI with another, non-class I-specific HDI presents a novel approach to the development of HDI’s as anti-cancer agents. Using this approach, an HDI combination therapy would have greater efficacy and possibly fewer side effects than any HDI used alone as a cancer therapy.
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