title: Histone deacetylase inhibition as an anticancer telomerase-targeting strategy.
abstract: Aberrant epigenetic regulation of gene expression contributes to tumor initiation and progression. Studies from a plethora of hematologic and solid tumors support the use of histone deacetylase inhibitors (HDACi) as potent anticancer agents. The mechanism(s) of HDACi-induced cancer growth inhibition and cell death are complex and incompletely elucidated. Here, we discuss erroneous epigenetic regulation of hTERT transcription in cancer cells and propose that alleviation of an improper acetylation-deacetylation balance at the hTERT promoter, is one mode by which HDACi induces anticancer effects. We conclude with some pertinent questions and future perspectives arising from the recent impetus in HDACi preclinical and early clinical studies, with particular attention to the cancer stem cell therapeutic paradigm and its relevance to tumor resistance.
authors.affiliation: Children's Brain Tumor Research Centre, University of Nottingham, UK. ruman.rahman@nottingham.ac.uk
authors.forename: Ruman
authors.initials: R
authors.lastname: Rahman
authors.forename: Richard
authors.initials: R
authors.lastname: Grundy
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D058990:Molecular Targeted Therapy; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000201:enzymology; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000187:drug effects* / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; C509186:TERT protein, human; D019098:Telomerase