Role of the hypoxic tumor microenvironment in the resistance to anti-angiogenic therapies

Drug Resist Updat. 2009 Jun;12(3):74-80. doi: 10.1016/j.drup.2009.03.002. Epub 2009 Apr 25.


Angiogenesis, a key process for the growth of human cancers, has recently been exploited for the development of a novel class of cancer therapeutics that was thought to have wide applications and not to induce resistance in the clinical setting. Indeed, anti-angiogenic therapy has become an important option for the management of several human malignancies. However, a significant number of patients either do not respond to anti-angiogenic agents or fairly rapidly develop resistance. In addition, the benefit of anti-angiogenic therapy is relatively short-lived and the majority of patients eventually relapses and progresses. Several mechanisms of resistance to anti-angiogenic therapy have been recently proposed. The current review focuses on the role of intra-tumor hypoxia as a mechanism of resistance to anti-angiogenic agents and speculates on therapeutic approaches that might circumvent resistance and thereby improve clinical outcome.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Angiogenesis Inhibitors / therapeutic use
  • Cell Hypoxia / drug effects*
  • Cell Hypoxia / physiology*
  • Combined Modality Therapy
  • Drug Resistance, Neoplasm / physiology*
  • Humans
  • Neoplasms / blood supply*
  • Neoplasms / drug therapy
  • Neoplasms / physiopathology*
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / physiopathology*


  • Angiogenesis Inhibitors