How do tumor cells respond to HDAC inhibition?

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 ( HDAC s), have been extensively studied and small‐molecule HDAC inhibitors ( HDAC 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 HDAC 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 HDAC i, including modulating tumor immunogenicity have also been described and may have substantial roles in mediating the antitumor effects of HDAC i. We posit that the field has failed to fully reconcile the biological consequences of exposure to HDAC is with the molecular events that underpin these responses, however progress is being made. Understanding the pleiotrophic activities of HDAC is on tumor cells will hopefully fast track the development of more potent and selective HDAC i that may be used alone or in combination to improve patient outcomes.