Angiogenesis in the News

Discussion of Angiogenesis Inhibitors in not new to this newsletter. We have been tracking Dr. Judah Folkman's work on angiogenesis inhibitors for several years. The hemangiomas of VHL are essentially the "food supply" of a cancer tumor, without the hard tumor itself. A hemangioma is that nest of abnormal blood vessels that you see in the diagrams, without the tumor part. In shrinking the nest of blood vessels, you shrink the hemangioma.

In 1994 a number of VHL Family Alliance members gave urine samples to Dr. Folkman to test for chemical tracers that would tell him whether angiostatin or endostatin might be effective in the treatment of VHL. The answer at that time was that those two drugs were not quite the right ones, but nonetheless the theory is exactly what we need -- we just need a more specific drug.

Angiogenic factors (those which lead to the development of new blood vessels, or hemangiomas) are

• hypoxia (when there is too little oxygen, the body builds more blood vessels to bring more blood to bring more oxygen),
• tissue injury (where increased blood flow is needed for repairs), and
• vascular endothelial growth factor (VEGF).

Thus the VHL protein is up-regulating an angiogenic factor and down-regulating an inhibitor of angiogenesis.

Through biomedical research at many institutions we are beginning to understand the function of the VHL protein and what drugs might be able to intervene in the chemical processes in the cell, bolster or replace the function of the missing VHL protein, and prevent the formation of tumors.

Dr. Edward Oldfield and others reported several years ago that VEGF, a powerful angiogenetic factor, was found in high quantities around brain and spinal tumors. Dr. Maartje Los reported to the Dutch VHL/MEN meeting in 1997 that VEGF is found in excessive quantities in the ocular fluid and renal cyst fluid of VHL patients, much higher than in the blood. These and other studies indicate that the VHL gene might be regulating VEGF expression in living tissues.

There are some new drugs which have been shown to manipulate the levels of VEGF in mice, and there is reason to believe that they might be helpful for people with VHL. "But it’s tricky," says Dr. Richard Klausner, Director of the National Cancer Institute. "The testing has to be very carefully conducted because we don’t want to cause bleeding. Testing these drugs on people with VHL is a delicate business, and will take at least a year. It won’t be as dramatic as what you have seen recently  in the news." The National Cancer Institute is now writing a protocol for use of one of these new drugs with renal cell carcinomas, including VHL. A similar study is expected to start in Boston for people with brain and spinal involvement in the fall.