Histone deacetylase inhibition as an anticancer telomerase-targeting strategy

Int J Cancer. 2011 Dec 15;129(12):2765-74. doi: 10.1002/ijc.26241. Epub 2011 Aug 8.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Cell Death / drug effects
  • Gene Expression Regulation, Enzymologic / drug effects
  • Histone Deacetylase Inhibitors / pharmacology*
  • Humans
  • Molecular Targeted Therapy
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / enzymology
  • Telomerase / antagonists & inhibitors*
  • Telomerase / drug effects*
  • Telomerase / metabolism
  • Tumor Cells, Cultured


  • Antineoplastic Agents
  • Histone Deacetylase Inhibitors
  • TERT protein, human
  • Telomerase