Targeting tumor angiogenesis with histone deacetylase inhibitors

Leigh Ellis, Hans Hammers, Roberto Pili

Research output: Contribution to journalShort survey

172 Scopus citations

Abstract

Solid tumor malignancies including breast, lung and prostate carcinomas are considered to be angiogenesis dependent. Tumor angiogenesis is often mediated by hypoxia secondary to tumor growth or by increased oncogenic signaling. Both mechanisms result in increased hypoxia-inducible factor-1 alpha (HIF-1α) signaling and its transcriptional target vascular endothelial growth factor (VEGF). Critical to HIF-1α signaling are post translational modifications including acetylation mediated by histone acetyltransferases (HATS) and deacetylation by histone deacetylases (HDACs). More recently, HDACs were shown to be up-regulated in response to hypoxia mediating increased HIF-1α signaling. HDAC inhibitors represent a new class of anti-cancer therapeutics which show great promise at inhibiting angiogenesis in pre-clinical animal models and early phase clinical trials. This review will discuss the role of HIF-1α and VEGF influence on tumor angiogenesis and how HDACs play a critical role in HIF-1α transcriptional activity. Furthermore it will also be discussed how targeting HDACs via their inhibition create new avenues in treating solid malignancies by increasing the activity of established and novel therapeutic applications.

Original languageEnglish (US)
Pages (from-to)145-153
Number of pages9
JournalCancer Letters
Volume280
Issue number2
DOIs
StatePublished - Aug 8 2009
Externally publishedYes

Keywords

  • Angiogenesis
  • Angiogenesis inhibitors
  • Animal models
  • Cancer
  • Clinical trials
  • Combination therapy
  • Gene regulation
  • HDAC
  • HDAC inhibitors
  • HIF-1α
  • Tyrosine kinase inhibitors
  • VGEF
  • mTOR inhibitors

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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