Judah Folkman (1933–2008)
In 1971, Judah Folkman at Harvard Medical School proposed an original approach to the treatment of cancer, a concept that was dismissed by experts in the field for years. He theorized that, in order to grow and spread, tumor cells need a rich blood supply that provides them with adequate oxygen and nutrients, and that as the tumor increases in size, its requirements for blood supply become greater.
This increase in blood supply is accomplished by the influence of vascular endothelial growth factor (VEGF), which, when released, stimulates the formation of new blood vessels, a process called angiogenesis. Folkman proposed that inhibiting VEGF would prevent the growth of blood vessels surrounding the tumor, starving it and, thus, exerting an anticancer effect.
Avastin (bevacizumad), manufactured by Genentech, was the first angiogenesis inhibitor developed that works by this mechanism. A biologic drug, its large and complex molecules are produced by approaches involving recombinant DNA technology.
Since 2004, Avastin has become the world’s best-selling anticancer drug, with annual sales of $6 billion in 2010. Used in combination with other antitumor drugs for the treatment of cancers of the colon, lung, kidney, and brain, Avastin was rapidly approved for the treatment of advanced breast cancer in the United States in 2008. To the dismay of many patients and their physicians, this approval was withdrawn in 2010, when the results of more detailed subsequent studies revealed that Avastin delayed tumor growth progression by only a few months, while subjecting patients to serious side effects. By contrast, the drug continues to be approved for use for advanced breast cancer in the European Union, based on the same information.
Because Avastin has been approved for marketing, physicians can continue to legally prescribe it on an off-label basis for breast cancer. However, insurance companies may no longer cover its $100,000 per year cost when prescribed for this condition. European drug regulatory authorities have, since 2010, permitted the manufacture of generic equivalents of Avastin and other biologic drugs (biosimilars).
SEE ALSO Off-Label Drug Use (1962), Biologic Drugs (1982), Herceptin (1998), Iressa and Erbitux (2003), Lucentis (2006).
To grow and spread, tumor cells need a generous supply of oxygen and nutrients, which are provided by a rich blood supply. Such increased growth of new blood vessels (vascularization) is seen here in the area of a uterine tumor. Avastin slows vascularization, producing its anticancer effects by starving the tumor.