Chapter 8: Histone Deacetylases

Histone deacetylases (HDAC) are enzymes that regulate biological activity through removal of acetyl groups from histones and non-histone proteins. A few HDAC inhibitors have been approved for use as anti-cancer agents, but their clinical uptake so far has been limited, presumably due to their adverse effect profiles. Consequently, a new generation of HDAC inhibitors has emerged with improved chemistry and pharmacological properties, optimised through mechanism of action and precision medicine strategies. In this chapter, we provide a brief history of HDAC biology and showcase a few notable HDAC inhibitors which have shown clinical promise in cancer and non-cancer indications. While interest in HDAC inhibitors has had its peaks and troughs, recent scientific discoveries intersecting epigenetics and immuno-oncology give us reason to believe that the therapeutic potential of HDAC inhibitors has yet to be fully realised. As the field advances, these next-generation HDAC inhibitors, coupled with their immunotherapy combinations, could very well become indispensable instruments in the fight against cancer and other diseases.