How do tumor cells respond to HDAC inhibition?

<jats:p>It is now well recognized that mutations, deregulated expression, and aberrant recruitment of epigenetic readers, writers, and erasers are fundamentally important processes in the onset and maintenance of many human tumors. The molecular, biological, and biochemical characteristics of a particular class of epigenetic erasers, the histone deacetylases (<jats:styled-content style="fixed-case">HDAC</jats:styled-content>s), have been extensively studied and small‐molecule <jats:styled-content style="fixed-case">HDAC</jats:styled-content> inhibitors (<jats:styled-content style="fixed-case">HDAC</jats:styled-content>is) have now been clinically approved for the treatment of human hemopoietic malignancies. This review explores our current understanding of the biological and molecular effects on tumor cells following <jats:styled-content style="fixed-case">HDAC</jats:styled-content>i treatment. The predominant responses include induction of tumor cell death and inhibition of proliferation that in experimental models have been linked to therapeutic efficacy. However, tumor cell‐intrinsic responses to <jats:styled-content style="fixed-case">HDAC</jats:styled-content>i, including modulating tumor immunogenicity have also been described and may have substantial roles in mediating the antitumor effects of <jats:styled-content style="fixed-case">HDAC</jats:styled-content>i. We posit that the field has failed to fully reconcile the biological consequences of exposure to <jats:styled-content style="fixed-case">HDAC</jats:styled-content>is with the molecular events that underpin these responses, however progress is being made. Understanding the pleiotrophic activities of <jats:styled-content style="fixed-case">HDAC</jats:styled-content>is on tumor cells will hopefully fast track the development of more potent and selective <jats:styled-content style="fixed-case">HDAC</jats:styled-content>i that may be used alone or in combination to improve patient outcomes.</jats:p>