Targeting hypoxia and angiogenesis through HIF-1alpha inhibition

Cancer Biol Ther. 2005 Oct;4(10):1055-62. doi: 10.4161/cbt.4.10.2195. Epub 2005 Oct 21.


Hypoxia is an important phenomenon in the tumor microenvironment. Hypoxic tumors are more aggressive and resistant to anti-neoplastic treatments. HIF-1alpha plays a major role in the response of tumors to hypoxia, and it is mainly responsible for the "angiogenic switch". HIF-1alpha contributes to tumor aggressiveness, invasiveness, and resistance to radiotherapy and chemotherapy. Targeting HIF-1alpha is an attractive strategy, with the potential for disrupting multiple pathways crucial for tumor growth. We review recent findings on the potential efficacy of small molecules to downregulate HIF-1alpha. These promising drugs inhibit HIF-1alpha synthesis or transcriptional activity by blocking a variety of steps in several different signaling pathways. Blocking HIF-1alpha activity should not only downregulate tumor angiogenesis, but also interfere with glycolytic metabolism and tumor cell growth. This strategy could also improve the efficiency of established tumor therapies.

Publication types

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

MeSH terms

  • Cell Hypoxia / physiology*
  • Gene Targeting*
  • Humans
  • Hypoxia-Inducible Factor 1 / antagonists & inhibitors*
  • Hypoxia-Inducible Factor 1 / genetics
  • Hypoxia-Inducible Factor 1 / metabolism
  • Models, Biological
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism*
  • Neovascularization, Pathologic / prevention & control


  • Hypoxia-Inducible Factor 1