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.