HDAC inhibitors: From bench to clinic, and back again


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Nicholas La Thangue1
1University of Oxford, Oxford, UK

Abstract

Histone deacetylase (HDAC) inhibitors are potent anti-proliferative agents, and there is a great deal of interest in HDAC inhibitor-based therapies as a new type of anti-cancer therapy. However, many details of the pathways through which HDAC inhibitors act remain to be determined, and consequently understanding their clinical utility has been hampered. We have explored the pathways affected by HDAC inhibitors, and exploited this information in the clinical context to develop strategies that allow responsive disease to be identified. Our work suggests proteostasis is a key level of control that is influenced by HDAC and HDAC inhibitors, and further that aberrant proteostasis has a significant impact on the outcome of therapeutic intervention. We will discuss our recent studies aimed at exploiting this information as predictive biomarkers, and the implications for developing HDAC inhibitors as a personalised cancer medicine.

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