Histone deacetylase inhibitors: current status and overview of recent clinical trials.
Histone deacetylase (HDAC) inhibitors are a new group of anticancer agents that have a potential role in the regulation of gene expression, induction of cell death, apoptosis and cell cycle arrest of cancer cells by altering the acetylation status of chromatin and other non-histone proteins. In clinical trials, HDAC inhibitors have demonstrated promising antitumour activity as monotherapy in cutaneous T-cell lymphoma and other haematological malignancies. In solid tumours, several HDAC inhibitors have been shown to be efficacious as single agents; however, results of most clinical trials were in favour of using HDAC inhibitors either prior to the initiation of chemotherapy or in combination with other treatments. Currently, the molecular basis of response to HDAC inhibitors in patients is not fully understood. In this review, we summarize the current status of HDAC inhibitors, as single agents or in combination with other agents in different phases of clinical trials. In most of the clinical trials, HDAC inhibitors were tolerable and exerted biological or antitumor activity. HDAC inhibitors have been studied in phase I, II and III clinical trials with variable efficacy. The combination of HDAC inhibitors with other anticancer agents including epigenetic or chemotherapeutic agents demonstrated favourable clinical outcome.
Ma
Xujun
X
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota 55905, USA.
Ezzeldin
Hany H
HH
Diasio
Robert B
RB
D000107:Acetylation / Q000187:drug effects; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D044127:Epigenesis, Genetic / Q000187:drug effects; D005544:Forecasting; D015870:Gene Expression / Q000187:drug effects; D051548:Histone Acetyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases