Angiogenesis plays an essential role during development and participates in homeostatic events in adulthood such as tissue repair and reproduction. 1 Angiogenesis is deregulated in certain pathologies described as ‘angiogenesis-dependent diseases’, including heart disease, macular degeneration, rheumatoid arthritis, hemangiomas and cancer. 2 Tumor growth depends on the formation and recruitment of new blood vessels caused by the expression of proangiogenic proteins within the tumor microenvironment including vascular endothelial growth factor-A (VEGF-A), basic fibroblast growth factor (bFGF), and interleukin-8 (IL-8). 3 During the ‘angiogenic switch’a number of negative endogenous regulators of angiogenesis, including thrombospondin-1 (TSP-1), endostatin, interferon alpha and tissue inhibitor of metalloproteinases (TIMPs) are downregulated. The discovery of proangiogenic molecules led to the development of synthetic angiogenesis inhibitors that target the tumor endothelium and inhibit tumor angiogenesis. In 2004, the Federal Drug Administration (FDA) approved bevacisumab (Avastin), the first antiangiogenic drug for metastatic colon cancer that targets and neutralizes VEGF-A, thereby inhibiting proliferation, migration and survival of vascular endothelial cells within the tumor microenvironment. The FDA has also approved several drugs with antiangiogenic activity including sorafenib (Nexavar), sunitinib (Sutent), pazopanib (Votrient), and everolimus (Afinitor), while others such as angiostatin, thrombospondin and endostatin remain in various stages of development. Studies have shown that the direct angiogenesis inhibitors are less toxic than other chemotherapeutic drugs, but not completely without side effects. Since they target normal endothelium and not tumor cells, they also have a lower risk of introducing drug resistance, although tumors may use genetic instability to switch or escape dependence on VEGF-A as a primary angiogenic stimulus. 4 There is, however, a group of angiogenesis inhibitors that have been shown to prevent angiogenesis indirectly via the disruption of oncogenic proteins in tumor cells, eg. receptor tyrosine kinases, that drive angiogenesis as part of their signaling pathways.