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Radiation Tackles Tumors on Two Fronts

cancerous cells



SCIENCE
A cancer diagnosis often brings with it a prescription for radiation therapy to kill diseased cells and shrink tumors. The underlying rationale for this course of treatment is that the high-energy radiation damages the DNA in a tumor mass, thereby arresting its growth. But the results of a study published today in the journal Science indicate that radiation therapy may actually attack tumors in two ways. Scientists report finding genetic evidence that radiation-induced damage to the blood vessels feeding a tumor plays a pivotal role in causing the mass to recede.

Monica Garcia-Barros of the Memorial Sloan-Kettering Cancer Center and her colleagues tested radiation therapy on genetically-engineered mice with cancerous tumors. Specifically, they looked at mice incapable of producing an enzyme known as acid sphingomyelinase. This enzyme is made in so-called endothelial cells, which cancer cells recruit from their host to form blood vessels to nourish the tumor. That process, known as angiogenesis, hit the headlines in 1998 when cancer researcher Judah Folkman of Harvard Medical School discovered two natural compounds that shrank tumors in mice by cutting off the blood supply. The researchers determined that animals incapable of producing the enzyme did not respond to radiation therapy nearly so well as their normal counterparts did. The reason for this, they surmise, is that acid sphingomyelinase regulates cell death in the delicate endothelial cells. Without it, they can resist the effects of radiation. Lacking this enzyme thus put the engineered mice at a disadvantage┬┐and revealed to the investigators that radiation attacks not only the tumor cells, but the endothelial cells that nourish them. Notes study co-author Richard Kolesnick of Sloan Kettering, "When the angiogenic blood vessels are damaged, the death of tumor cells results."

The authors hope their findings will lead to improvements in patient care, perhaps by helping researchers find ways to prime tumors to succumb to lower doses of radiation. Zvi Fuks, another co-author of the study, explains: "We need to understand, at the therapeutic dose range, the unique roles that the microenvironment and tumor cell components play in the overall response of the tumor to radiation to maximize the value of such treatments."

"Vessels of Death and Life," by Rakesh K. Jain and Peter F. Carmeliet; Scientific American, December 2001, is available for purchase at the Scientific American Archive.
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