Inhibition of vascular endothelial growth factor in the treatment of solid tumors.
Vascular endothelial growth factor (VEGF) is the term used for a family of tumor-derived angiogenic factors that mediate endothelial proliferation and vascular permeability. Preclinical models have demonstrated the essential nature of VEGF in the angiogenesis of solid tumor growth and metastasis, whereas pathologic investigations have revealed strong correlations between VEGF production, microvessel density, and overall aggressiveness of many human solid tumors. Recent advances in the understanding of the molecular mechanisms of VEGF action have led to successful models for intervention in VEGF-mediated pathways in therapy for solid tumors. These include antibodies to block the binding of VEGF to its cellular receptors, small-molecule chemical inhibitors of the tyrosine kinase functions of the VEGF receptors, and antisense nucleic acids to interfere with cellular production of VEGF. Clinical investigations are ongoing to test the value of VEGF-based intervention alone or in combination with other anticancer agents.
Margolin
Kim
K
Departments of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA 91010, USA. kmargolin@coh.org
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004351:Drug Resistance; D016228:Endothelial Growth Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008222:Lymphokines / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy*; D020794:Receptor Protein-Tyrosine Kinases / Q000187:drug effects; D017978:Receptors, Growth Factor / Q000187:drug effects; D040262:Receptors, Vascular Endothelial Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; 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