In addition to killing cells directly, radiation also stops angiogenesis, the growth of blood vessels that are essential for a tumor's growth, says a report in the May 16 issue of Science. This is the first genetic evidence that damage to the blood vessels that feed a cancer can cause that cancer to shrink, say researchers from the Memorial Sloan-Kettering Cancer Center in New York City.
Dr. Judah Folkman of Harvard Medical School proposed the theory several years ago that stopping angiogenesis could be an effective way to treat cancer. However, that theory remains controversial because a number of trials aimed at stopping angiogenesis in cancer patients have produced mixed results.
Radiation kills cancer cells directly. But working with genetically engineered mice, the researchers showed that it damages cells other than those of the cancer -- the delicate endothelial cells that line blood vessels and are essential to their function.
The mice were manufactured to be deficient in an enzyme called acid sphingomyelinase, which regulates apoptosis, the process of natural endothelial cell death.
Cells of two kinds of cancer, melanoma and fibrosarcoma, were implanted in those mice. The tumors grew at twice the rate seen in normal mice. And the cancers did not shrink when the mice were exposed to radiation, as would normally happen.
The new study arose from previous work indicating that damage to small blood vessels played a role in the injury caused to the gastrointestinal tract caused by radiation, says a statement by Dr. Richard Kolesnick, head of Memorial Sloan-Kettering's signal transduction laboratory and a leader of the research team.
"It was unclear that this would also happen in tumors," Kolesnick says. "Our new study shows that damaging the angiogenic blood vessels of the tumor does indeed contribute to tumor regression."
There are several ways the finding could be used to improve cancer treatment, says Dr. Carlos Cordon-Cardo, director of the Memorial-Sloan Kettering division of molecular pathology and a member of the research team.
"Knowing that these blood vessels respond to specific factors, we can aim therapy at those factors," he says.
And it may be possible to combine anti-angiogenesis therapy with radiation therapy that is aimed not at the cancer cells themselves but at the factors that promote blood vessel growth, Cordon-Cardo says.
But more research is needed to determine such important factors as the exact role radiation treatment would play in such combined therapy and the most effective radiation doses, the researchers say.