title: Histone deacetylase inhibitors: emerging anticancer therapeutic agents?
abstract: 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.
authors.affiliation: Institute for Cancer Research and Royal Marsden Hospital, Surrey, UK.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Kristeleit
authors.forename: Peter
authors.initials: P
authors.lastname: Fong
authors.forename: G Wynne
authors.initials: GW
authors.lastname: Aherne
authors.forename: Johann
authors.initials: J
authors.lastname: de Bono
mesh_terms: 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
chemical_list: D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D009707:Nucleosomes; D020033:Protein Isoforms; D006655:Histone Deacetylases