Discovery and Development of Antiangiogenesis Drugs.
In 1961, a young surgeon, Dr. Judah Folkman, noted that cancer cells injected in vitro in thyroid preparations grew to small tumors and then stopped. However, when implanted into mice, the same cells grew into massive tumors. Folkman realized that the in vivo tumors had the advantage of a newly formed, rich vascular bed and blood supply, which the tumor had recruited (Katzung, Masters, & Trevor, 2009). In his 1971 landmark paper, Dr. Folkman concluded that if we could turn this process off, the tumors should remain small. In 1984, Folkman described the first angiogenic factor and in 1997, endostatin, an antiangiogenic factor. In 1989, Ferrera and colleagues described the vascular endothelial growth factor (VEGF) and in 1993, they were able to block the VEGF using a mouse antibody. Although first clinical trials failed, research continued until 2004 when Bevacizumab (Avastin) became the first antiangiogenesis drug to receive FDA approval. The cost of its research and development (by Genentech) was $2.25 billion. The potential advantages of this type of therapy, particularly with antibodies, are an enhanced target selectivity and a toxicity profile significantly milder than that of cytotoxic drugs (Katzung et al., 2009).
Why is Angiogenesis important in cancer?.
Angiogenesis is the process of formation of new blood vessels. It is controlled by certain chemicals produced in the body that stimulate the cells to repair damaged blood vessels or form new ones (National Cancer Institute, 2008). In adults, new blood vessel growth is normally limited to areas of wound healing and to the female uterus during the proliferative phase of the menstrual cycle. Angiogenesis plays an important role in the growth and spread of cancer because, as cancer grows, it needs its own blood supply to receive oxygen and nutrients. Malignant tumors, especially those in metastatic sites, can secrete factors that induce the formation of new blood vessels (angiogenic factors), which serve as routes for the transport of the nutrients into the tumor.
