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Factor may halt spread of cancer

Researchers have discovered a natural hormone-like factor that keeps tumor growth under control. The find may rank among the most important advances against cancer in recent decades.

Although it is not a cure for cancer, researchers in Boston said the factor could eventually become a potent anti-cancer weapon, a natural drug able to control the explosive growth of metastases, the tiny malignant "seeds" that spread cancer throughout the body.

These secondary tumors, which can settle in vital organs such as the lungs, liver, bones and brain, are often more deadly than the original, killing patients even after the main tumor has been removed.

The growth-inhibiting factor, called angiostatin, was discovered first in mice, then in humans by Dr. Michael O'Reilly, working with Dr. Judah Folkman at Children's Hospital. The scientists reported the new findings Friday in the scientific journal Cell.

Apparently non-toxic, the newly found factor is produced by large, growing tumors such as those found in breast and colorectal cancers. It circulates through the bloodstream, apparently acting as a brake on the growth of microscopically small secondary tumors elsewhere in the body.

Once the primary tumor is removed, however, the brakes disappear and the tiny, invisible tumors begin the uncontrolled growth characteristic of metastatic cancer.

Although angiostatin has not yet been tested in humans, O'Reilly's experiments with mice show that the factor is very powerful. Injections of angiostatin completely blocked the growth of secondary tumors that normally would have killed the animals within weeks.

The team also saw evidence that its growth inhibitor can block the growth of large primary tumors. "We used it to treat two different primary tumors in mice . . . both of which go to the lungs," O'Reilly said. The result, he said, was that "it was very effective in treating primary tumors as well."

"We're still refining the dose levels," he said, "but our early studies show a high degree of efficacy."

Scientists familiar with the Boston team's work called the discovery a landmark.

Patricia Steeg, chief of the women's cancer section for laboratory pathology at the National Cancer Institute in Bethesda, Md., said the finding is "spectacular . . . an example of the future in anti-cancer therapy, which is to find the body's own ways of counteracting cancer cells."

Dr. Isaiah Fidler, chairman of biology at the M.D. Anderson Cancer Center in Houston, a world leader in studying metastasis, said the results are "of immense importance," particularly if angiostatin works against a wide variety of tumor types.

But even if it does work as hoped, getting angiostatin into general use could take as long as a decade, experts say.

The next step is to create a large enough supply to allow the scientists to expand ongoing animal experiments, assessing the growth inhibitor's safety, determining dosage levels and seeing if the tumor-suppressing effect can be prolonged.

If successful, angiostatin would then have to undergo three stages of clinical trials on human beings.