A review of the latest clinical compounds to inhibit VEGF in pathological angiogenesis

Expert Opin Ther Targets. 2006 Dec;10(6):867-76. doi: 10.1517/14728222.10.6.867.

Abstract

Angiogenesis plays an important role in the formation of new blood vessels and is crucial for tumour development and progression. Imbalance between pro- and antiangiogenesis factors regulates the biological process of angiogenesis. The best characterised of the proangiogenic factors and the most potent is vascular endothelial growth factor (VEGF). The binding of VEGF to one of its transmembrane tyrosine kinase receptors, which are predominantly found on endothelial cells, results in receptor dimerisation, activation and autophosphorylation of the tyrosine kinase domain. This triggers a cascade of complex downstream signalling pathways. Several strategies targeting the VEGF signalling pathway have been developed. These include neutralising antibodies to VEGF (bevacizumab) or VEGF receptors (VEGFRs) (DC101), soluble VEGFR/VEGFR hybrids (VEGF-Trap), and tyrosine kinase inhibitors of VEGFRs (BAY43-9006, SU11248, ZD6474, AZD2171, PTK/ZK and others). Several of these agents are now being investigated in clinical trials.

Publication types

  • Review

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Angiogenesis Inhibitors / therapeutic use
  • Clinical Trials as Topic
  • Humans
  • Neovascularization, Pathologic / drug therapy*
  • Vascular Endothelial Growth Factors / antagonists & inhibitors*
  • Vascular Endothelial Growth Factors / metabolism

Substances

  • Angiogenesis Inhibitors
  • Vascular Endothelial Growth Factors