Angiogenesis in metastatic colorectal cancer and the benefits of targeted therapy

The diverse pathways and molecules involved in angiogenesis, the formation of new blood vessels, have been targeted for the treatment of colorectal and other cancers. Vascular endothelial growth factor (VEGF)-A binding to VEGF receptor (VEGFR)-2 is believed to be the key signaling pathway mediating angiogenesis. Other VEGF pathways involved in angiogenesis include VEGF-A, VEGF-B, and placental growth factor binding to VEGFR-1, and VEGF-C and VEGF-D binding to VEGFR-2 and VEGFR-3. VEGF signaling also intersects with other pathways, including angiopoietin/Tie, Notch, hypoxia-inducible factor, and integrin pathways. The roles of these pathways in tumor angiogenesis and in various human cancers will be explored in this article. In addition, preclinical and clinical data on bevacizumab, aflibercept (known as ziv-aflibercept in the US), and investigational antiangiogenic agents in development for the treatment of colorectal and other cancers will be reviewed.