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Cancer Epigenetics: Mechanisms and Crosstalk of a HDAC Inhibitor, Vorinostat

Jean Lee and Stephanie Huang R

In recent years, histone deacetylase inhibitors (HDACis), a novel class of agents that targets mechanistic abnormalities in cancers, have shown promising anti-cancer activity in both hematological and solid cancers. Among them, vorinostat was approved by FDA to treat cutaneous T-cell lymphoma and is being evaluated in other cancer types. Although initially designed to target histone deacetylase, vorinostat were found to have additional effects on other epigenetic machineries, for example acetylation of non-HDAC, methylation and microRNA (miRNA) expression. In this review, we examined all known mechanisms of action for vorinostat. We also summarized the current findings on the ‘crosstalk’ between different epigenetic machineries. These findings suggest that improved understanding of epigenetic regulatory role of vorinostat and/or other HDACis will provide novel insights in improving utilization of this class of novel agents.