VEGF and angiopoietin signaling in tumor angiogenesis and metastasis.

Solid tumors require blood vessels for growth and dissemination, and lymphatic vessels as additional conduits for metastatic spread. The identification of growth factor receptor pathways regulating angiogenesis has led to the clinical approval of the first antiangiogenic molecules targeted against the vascular endothelial growth factor (VEGF)-VEGF receptor (VEGFR)-2 pathway. However, in many cases resistance to anti-VEGF-VEGFR therapy occurs, and thus far the clinical benefit has been limited to only modest improvements in overall survival. Therefore, novel treatment modalities are required. Here, we discuss the members of the VEGF-VEGFR family as well as the angiopoietin growth factors and their Tie receptors as potential novel targets for antiangiogenic and antilymphangiogenic therapies.