Targeting histone deacetylases for cancer therapy: from molecular mechanisms to clinical implications

Int J Biol Sci. 2014 Jul 2;10(7):757-70. doi: 10.7150/ijbs.9067. eCollection 2014.

Abstract

Genetic abnormalities have been conventionally considered as hallmarks of cancer. However, studies over the past decades have demonstrated that epigenetic regulation also participates in the development of cancer. The fundamental patterns of epigenetic components, such as DNA methylation and histone modifications, are frequently altered in tumor cells. Acetylation is one of the best characterized modifications of histones, which is controlled by histone acetyltransferases (HATs) and histone deacetylases (HDACs). HDACs are a group of enzymes which catalyze the removal of the acetyl groups of both histones and non-histone proteins. HDACs are involved in modulating most key cellular processes, including transcriptional regulation, apoptosis, DNA damage repair, cell cycle control, autophagy, metabolism, senescence and chaperone function. Because HDACs have been found to function incorrectly in cancer, various HDAC inhibitors are being investigated to act as cancer chemotherapeutics. The primary purpose of this paper is to summarize recent studies of the links between HDACs and cancer, and further discuss the underlying mechanisms of anti-tumor activities of HDAC inhibitors and clinical implications.

Keywords: HDAC; HDAC inhibitor; cancer.; epigenetic therapy.

Publication types

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

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis
  • Autophagy
  • Cell Cycle
  • Cellular Senescence
  • DNA Repair
  • Gene Expression Regulation
  • Histone Deacetylase Inhibitors / pharmacology
  • Histone Deacetylase Inhibitors / therapeutic use*
  • Histone Deacetylases / metabolism
  • Histone Deacetylases / physiology*
  • Models, Biological

Substances

  • Antineoplastic Agents
  • Histone Deacetylase Inhibitors
  • Histone Deacetylases