HDAC inhibitors and cancer therapy

Maintenance of normal cell growth and differentiation is highly dependent on coordinated and tight transcriptional regulation of genes. In cancer, genes encoding growth regulators are abnormally expressed. Particularly, silencing of tumor suppressor genes under the control of chromatin modifications is a major underlying cause of unregulated cellular proliferation and transformation. Thus mechanisms, which regulate chromatin structure and gene expression, have become attractive targets for anticancer therapy. Histone deacetylases are enzymes that modify chromatin structure and contribute to aberrant gene expression in cancer. Research over the past decade has led to the development of histone deacetylase inhibitors as anticancer agents. In addition to their effect on chromatin and epigenetic mechanisms, HDAC inhibitors also modify the acetylation state of a large number of cellular proteins involved in oncogenic processes, resulting in antitumor effects. The current monograph will review the role of histone deacetylases in protumorigenic mechanisms and the current developmental status and prospects for their inhibitors in cancer therapy.