New Studies on Tumor Blood Vessels
Two new studies have provided additional insight into one of the most promising areas of cancer research—attacking the blood vessels of tumors rather than the actual tumors themselves. By doing so, tumors are deprived of their blood supply, effectively starving them to death.
The first study, published in the journal Cancer Research, reported on a gene called RB2 that appears to inhibit the growth of new vessels in tumors, essentially cutting off their blood supply.
In experiments with laboratory animals, an international team of investigators led by Dr. Antonio Giordano monitored levels of a cancer marker called VEGF (vascular endothelial growth factor) that is present in aggressively growing tumors. When the researchers inserted the RB2 gene into the tumors, VEGF levels shrank—as did the tumors.
The researchers said that the presence of RB2 serves as a brake for the growth of new tumor blood vessels. When it is present, growth is inhibited; in its absence, new blood vessel growth commences unchecked.
More research is needed, they said, to find a more efficient way of inserting the RB2 gene into tumors, as well as to test for its safety in humans. But, according to Giordano, the technique holds incredible promise as a "biological drug" that could be used along with conventional cancer therapies in the coming years.
In a second study, Dr. Judah Folkman of the Harvard Medical School reported on special types of tumor-feeding blood vessels called mosaic tumor vessels. Writing in the journal Proceedings of the National Academy of Sciences, he said that blood samples from these vessels may hold the key to detecting cancer in its very earliest stages.
Mosaic tumor vessels are different than normal tumor vessels in that they contain both normal cells and cancer cells embedded in the vessel wall. Folkman says that some of these tumor cells will eventually be dislodged from the vessel wall—as many as 50 percent of them daily—representing one mechanism by which cancer migrates to other sites in the body.
Folkman believes that a unique genetic blood test could be developed that would specifically detect these cancer cells as they are being shed from the mosaic tumor vessel walls. If such cancer cells are found, that means that mosaic tumor vessels are present somewhere in the body—and are feeding a currently undetected tumor.
In effect, Folkman said, this technique would detect the presence of cancer far earlier than conventional tests available today. It would be especially valuable for high-risk patients, he noted, such as women with a strong family history of the disease.
The idea of targeting a tumor’s blood vessels (rather than the tumors themselves) was first introduced by Folkman way back in 1971—and it was virtually ignored. Writing in the New England Journal of Medicine, he suggested that by directly attacking the blood vessels that supply nutrients to tumors, the tumors would in effect be starved into submission, ceasing to grow and eventually dying.
Sound simple? Actually it was nothing short of revolutionary.
Folkman labored almost alone in the field of "angiogenesis inhibitors" for years. (Angiogenesis is the process by which new blood vessels are formed. Angiogenesis inhibitors act to interrupt this process.)
However, in the mid-1990s Folkman was able to complete a series of successful experiments in laboratory animals using a protein called endostatin, which was remarkably effective at hindering blood vessel growth in cancerous tumors. Importantly, it did not affect the growth of normal blood vessels.
The implications of Folkman’s findings were immense. But a temporary setback occurred in the fall of 1998 when scientists from the National Cancer Institute were not able to reproduce his results. However, in February 1999, a new National Cancer Institute team was finally able to duplicate his findings by actually traveling to his lab in Boston to conduct the experiments.
It took a quarter of a century, but the field of cancer research is finally taking Folkman’s approach seriously—with a vengeance. There are now at least 35 so-called anti-angiogenesis therapies being evaluated in clinical trials, and dozens more are on the immediate horizon.
Controlling the growth of cancerous blood vessels has been called one of the great scientific challenges of current medicine. But harnessing the mechanism of angiogenesis, or at least being able to subdue blood vessel growth in a targeted fashion, has ramifications far beyond cancer research. It has extraordinary implications for cardiovascular disease and many other ailments.
In the next few years, additional angiogenesis inhibitors will be reaching the clinical trial stage. And some researchers are predicting that the first of these blood vessel destroyers may become commercially available within as little as five years, if not sooner.
SOURCES:
Cancer Research, January, 2001; American Association for Cancer Research (http://www.aacr.org)
Proceedings of the National Academy of Sciences, January 16, 2001; 98:398-400
New England Journal of Medicine, 1971; 285:1182-1186
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