Targeting vascular endothelial growth factor (VEGF) for anti-tumor therapy, by anti-VEGF neutralizing monoclonal antibodies or by VEGF receptor tyrosine-kinase inhibitors.
Vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) is an important mediator of tumor-induced angiogenesis and represents a potential target for innovative anticancer therapy. In several animal models, neutralizing anti-VEGF/VPF antibodies have shown encouraging inhibitory effects on solid tumor growth, ascites formation and metastatic dissemination. Targeting the VEGF signaling pathway by means of VEGF receptor tyrosine-kinase inhibitors has shown similar efficacy in animal tumor models. Several of these anti-VEGF therapies are currently being tested in clinical trials in cancer patients. The profiles and effects of the neutralizing anti-VEGF/VPF antibodies and the VEGF receptor tyrosine-kinase inhibitors in animal models are reviewed and of the risks and benefits of VEGF blockade by one or the other treatments are discussed.
Schlaeppi
J M
JM
Core Technology, Novartis Pharmaceuticals, Novartis Limited, Basle, Switzerland. jean-marc.schlaeppi@pharma.novartis.com
Wood
J M
JM
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016228:Endothelial Growth Factors / Q000276:immunology* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D008222:Lymphokines / Q000276:immunology* / Q000502:physiology; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology; D017978:Receptors, Growth Factor / Q000037:antagonists & inhibitors* / Q000502:physiology; D040262:Receptors, Vascular Endothelial Growth Factor; D011994:Recombinant Proteins / Q000627:therapeutic use; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D016228:Endothelial Growth Factors; D004791:Enzyme Inhibitors; D008222:Lymphokines; D017978:Receptors, Growth Factor; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor