The Direct Effects of Anti–Vascular Endothelial Growth Factor Therapy on Tumor Cells

The vascular endothelial growth factor (VEGF) family members are essential mediators of tumor angiogenesis. The multiple functions of the VEGFs are mediated through complex interactions between their ligands, the high-affinity tyrosine kinase receptors, and co-receptors (neuropilins). Emerging evidence has shown that these receptors, formerly described as being exclusively expressed on endothelial cells, are also expressed on a number of nonendothelial cells, including tumor cells. Moreover, it has been shown that their receptors (VEGFRs) are functional in a number of nonendothelial systems, where they can serve as targets for anti-VEGF therapy. As the expression of VEGFRs on tumor cells contributes to the understanding of the complex roles of VEGF within the tumor microenvironment and elucidation of VEGF activity might further refine antineoplastic regimens, this article will review the main effects and selective interactions of the VEGFRs, the evidence for their expression and function on tumor cells, and the direct efforts of anti-VEGF therapy on tumor cells.