Radiation may target tumors' 'food,' too

Researchers have found that radiation therapy not only kills cancer cells directly, it also starts a process that destroys key cells in the tiny blood vessels that feed tumors.

"This research should provide a new dimension to solid-tumor therapy," said Dr. Zvi Fuks, an author of the paper published Friday in the journal Science. He practices at Memorial Sloan-Kettering Cancer Center in New York City.

Fuks noted that researchers have been looking in vain for 45 years for drugs that will make tumor cells more sensitive to radiation. "We find things that work in a Petri dish, but when you go to patients, they don't work."

The researchers established this lesser-known result of radiation therapy by genetically inactivating an enzyme, called acid sphinglomyelinase. Tumors growing in mice that lacked the enzyme were resistant to radiation and did not shrink after being exposed to low doses. The same tumors growing in mice that had the enzyme showed a normal response when dosed with radiation.

The cells lining the walls of the blood vessels are essential to the growth of a tumor, establishing new blood vessels that provide oxygen and nutrients in a process called angiogenesis. But when radiation hits the enzyme, it sets in motion the natural death of these cells.

Most radiation therapy, which about 50 percent of all cancer patients receive, has focused on attacking the tumor cells themselves, but the findings should change that.

If the supporting structure of tumors can be made more susceptible, shrinking and eliminating tumors can be accomplished.

"The ability to deprotect the blood vessels will provide new targets for tumor therapy," said Fuks.

The team has been working for a number of years to understand the microenvironment surrounding tumors to find new points of attack.

"Advances in tumor biology will sharpen the focus of clinical treatments and provide much needed scientific background for new approaches to cancer therapy," Fuks said.

For now, Fuks said, researchers need to learn more about the timing and dosing of radiation to maximize the effect against the blood vessels, as well as how that treatment might combine with other new cancer-fighting agents that attack tumors' blood supply.

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