Histone deacetylase inhibitors in cancer therapy.
OBJECTIVE
The purpose of this review is to provide an overview of recent advances in the development of histone deacetylase inhibitors (HDACi) for the treatment of cancer.


RESULTS
Recently, there has been a dramatic expansion of HDACi clinical investigation. There are now 11 HDACi in clinical trial, including inhibitors with a broad spectrum of HDAC isoform inhibitory activity as well as drugs with isoform selectivity. Over 70 combination therapy trials are in progress. Major areas of progress covered include the entry of new HDAC inhibitors into clinical development, recent progress in understanding of molecular mechanisms of HDACi anticancer activity, and a preclinical and clinical update on HDACi in combination.


CONCLUSIONS
In the period under review there have been advances in understanding of HDACi mechanisms of action, identification of rational combinations that address increased efficacy and overcoming resistance, and greatly expanded clinical development of pan-HDAC-inhibitory and isoform-selective inhibitors in monotherapy and combination therapy protocols.
Medical Oncology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland 20892, USA.
Min-Jung
MJ
Lee
Yeong Sang
YS
Kim
Shivaani
S
Kummar
Giuseppe
G
Giaccone
Jane B
JB
Trepel
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D002626:Chemistry, Pharmaceutical / Q000379:methods / Q000639:trends; D002986:Clinical Trials as Topic; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D056572:Histone Deacetylase Inhibitors; D006657:Histones / Q000378:metabolism; D006801:Humans; D007107:Immune System; D008495:Medical Oncology / Q000379:methods / Q000639:trends; D008956:Models, Chemical; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D014411:Neoplastic Stem Cells; D020033:Protein Isoforms
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D020033:Protein Isoforms