Blocked. New therapy induces a blood vessel-filling clot in a mouse's tumor.

Cutting Cancer's Supply Lines

Traditional cancer treatments attack the malignant cells directly, with surgery, radiation, or chemotherapy. But two studies to be reported tomorrow advance a promising new strategy: cutting off the blood vessels that deliver the oxygen and nutrients that tumors need to live and grow.

Philip Thorpe and his co-workers at the University of Texas Southwestern Medical Center in Dallas will report in Science that they can shrink or even eliminate tumors in mice with agents that trigger blood-clot formation in tumor-feeding vessels. And in Cell, Judah Folkman and his colleagues at Harvard Medical School describe the discovery of a natural compound that, by blocking the growth of new blood vessels in a tumor, can shrink large tumors down to microscopic size in mice.

To see tumors shrink so dramatically is ''outstanding ... better than my best hopes,'' says Noel Bouck of Northwestern University, who is also working on similar drugs. ''If it just works for human tumors, it will be fabulous.'' That's a big ''if,'' of course, but the strategy has a key advantage over many anticancer drugs, which falter as the cancer cells mutate into resistant forms. The cells of a tumor's blood vessels--the target of the new therapies--are normal and thus less prone to mutate than are cancer cells.

Both the Thorpe and Folkman teams' results build on 20 years' work, much of it from the Folkman group itself, showing that tumors not only need new blood vessels to grow, but secrete factors that stimulate blood-vessel formation. Since then, researchers have identified compounds that block the vessel growth, several of which are in early clinical trials. Now, the Folkman team has purified the most potent of these factors so far, which is secreted for unknown reasons by the cancer cells themselves.

Called endostatin, it attacked a wide variety of tumors in mice. When the animals were taken off the drug, the cancers regrew, but the treatment never lost its effectiveness. Each time it was restarted, the tumors shrank back to microscopic size. That result is ''unprecedented,'' says tumor biologist Bob Kerbel of the Sunnybrook Health Science Center at the University of Toronto. ''That would just never happen with chemotherapy.''

Thorpe took a different approach: destroying existing tumor blood vessels by inducing the cells lining them to make class II antigen, a protein they normally don't make. The researchers then took antibodies to class II antigen and linked them to a shortened version of another protein that triggers blood clotting. The team reasoned that by linking this protein to the antibody, they could direct it to the walls of the tumor blood vessels, causing clots to form specifically in those vessels.

The experiment ''worked like a charm,'' says Thorpe: The tumors were largely dead within 48 hours. But only the clinical trials planned for the next few years can show whether these charms will work for humans.

For more details, Science Online subscribers can link to the News story in today's Science.

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