Clinical development of angiogenesis inhibitors to vascular endothelial growth factor and its receptors as cancer therapeutics.
Angiogenesis, the formation of new blood vessels, is essential for both tumor growth and metastasis. Recent advances in our understanding of the molecular mechanisms underlying the angiogenesis process and its regulation have led to the discovery of a variety of pharmaceutical agents with anti-angiogenic activity. The potential application of these angiogenesis inhibitors is currently under intense clinical investigation. Compelling evidence suggests that vascular endothelial growth factor (VEGF) and its receptors play critical roles in tumor-associated angiogenesis, and that they represent potential targets for therapeutic intervention. This has been demonstrated in a variety of animal tumor models in which disabling the function of VEGF and its receptors was shown to inhibit both tumor growth and metastasis. A number of agents designed specifically for targeting VEGF and/or its receptors are being evaluated in various clinical trials in cancer patients. This review will discuss the biology of the VEGF and its receptors, the mechanisms of action as well as the current status in clinical development of antagonistic agents to VEGF and its receptors. Included in this review are antagonistic antibodies, ribozymes, immunotoxins, and synthetic small molecular inhibitors.
ImClone Systems Incorporated, 180 Varick Street, New York, NY 10014, USA. zhenping@imclone.com
Zhenping
Z
Zhu
Peter
P
Bohlen
Larry
L
Witte
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D016228:Endothelial Growth Factors / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000502:physiology; D006801:Humans; D008222:Lymphokines / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000502:physiology; D017978:Receptors, Growth Factor / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000502:physiology; D040262:Receptors, Vascular Endothelial Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D020533:Angiogenesis Inhibitors; D016228:Endothelial Growth Factors; D008222:Lymphokines; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor