Tumor and stromal pathways mediating refractoriness/resistance to anti-angiogenic therapies

Trends Pharmacol Sci. 2009 Dec;30(12):624-30. doi: 10.1016/j.tips.2009.09.004.


Identification and characterization of VEGF as an important regulator of angiogenesis, and FDA approval of the first anti-angiogenic drugs, has enabled significant advances in the therapy of cancer and neovascular age-related macular degeneration. However, similar to other therapies, inherent/acquired resistance to anti-angiogenic drugs may occur in patients, leading to disease recurrence. Recent studies in several experimental models suggest that tumor and non-tumor (stromal) cell types may be involved in the reduced responsiveness to the treatments. The present review examines the role of tumor- as well as stromal cell-derived pathways involved in tumor growth and in refractoriness to anti-VEGF therapies.

Publication types

  • Review

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Angiogenesis Inhibitors / therapeutic use
  • Animals
  • Drug Resistance, Neoplasm*
  • Humans
  • Neoplasms / blood supply*
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Stromal Cells / metabolism
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors


  • Angiogenesis Inhibitors
  • Vascular Endothelial Growth Factor A