Malignant tumors cannot grow beyond a certain size without essential nutrients and oxygen. Angiogenesis is a key process in tumor growth and spread in which tumors provoke the growth of new blood vessels to the tumor from pre-existing vessels; these new blood vessels provide the tumor with oxygen and nutrients, allowing these cells to grow, invade nearby tissue and spread to other parts of the body. To induce angiogenesis, tumors secrete various growth factors, such as VEGF, which send chemical signals to existing blood vessels to stimulate the growth of new blood vessels.
Currently available angiogenesis inhibitors are designed to stop the effects of the protein VEGF on tumors, interfering with the development of new blood vessels and blocking the supply of oxygen and nutrients that the tumor needs to grow and spread. However, studies have shown that resistance to VEGF inhibitors is associated with higher expression of additional growth factors, in particular members of the FGF and angiopoietin families. Simultaneous inhibition of VEGFR, FGFR, and the angiopoietin 1 receptor (Tie2) is expected to provide more potent inhibition of angiogenesis that is less prone to resistance than blocking VEGF alone.