The clinical landscape of HDAC inhibitors

There are eleven human isoforms of the zinc-dependent histone deacetylases (HDACs). These proteins are involved in the removal of acetyl and fatty acid acyl chains from polyamines and lysine residues in proteins. Of particular importance is histone deacetylation, the inhibition of which leads to transcriptional activation. Over the last two decades, many small molecule HDAC inhibitors have reached clinical development, with five approved drugs to date in oncology. This chapter reviews the recent progress in HDAC inhibitor therapy and discusses how isoform selectivity is central to exploiting the therapeutic potential of these compounds in cancer as well as other indications.