Histone deacetylase inhibitors: emerging anticancer therapeutic agents?
Histone deacetylase inhibitors are novel anticancer agents in clinical development that target the family of histone deacetylase (HDAC) enzymes responsible for deacetylating core nucleosomal histones and other proteins. The precise mechanisms resulting in the antiproliferative biologic effects of these agents are not yet known, but there are several proposed mechanistic models, including transcriptional and nontranscriptional processes. Clinical experience with these agents indicates that they are generally well tolerated, and anticancer activity has been observed in early clinical trials in several tumor types including non-small-cell lung cancer. The development of these agents continues, with an emphasis on the discovery of HDAC isoform-selective compounds. Successful future development relies on clearer understanding of the dominant mechanisms involved in the observed antiproliferative effects.
Kristeleit
Rebecca
R
Institute for Cancer Research and Royal Marsden Hospital, Surrey, UK.
Fong
Peter
P
Aherne
G Wynne
GW
de Bono
Johann
J
D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D049109:Cell Proliferation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D009707:Nucleosomes; D020033:Protein Isoforms
D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D009707:Nucleosomes; D020033:Protein Isoforms; D006655:Histone Deacetylases