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Histone deacetylase inhibitors: recent outcomes from clinical trials and the implications for oncology treatment approaches

Alexandra MR Marsh, Ruth Narramore, Keith Chapple, Alan J Lobo, Jonathan RL Wild, Bernard M Corfe

Histone deacetylases play an important role in multiple processes, including gene expression, proliferation, apoptosis, cytoskeletal organization, migration and angiogenesis. Histone deacetylase inhibitors are able to induce cell death and growth arrest as targeted anticancer agents. Whilst only two, vorinostat and romidepsin, are licensed in oncology, several have reached Phase III trials and many more are in Phase I and II. In addition to this, multiple novel drugs, including more targeted agents, are emerging from preclinical studies. This paper examines the outcomes of recent clinical trials in 11 key histone deacetylase inhibitors, both as monotherapy and in combination with other antitumor drugs. An overview of the advantages and disadvantages between the different classes and individual drugs is discussed, as well as a brief outlook on the future developments in the field.