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Gene Therapy Targets Colon Cancer

Technique shrinks tumors, slows disease's spread in rats

TUESDAY, Feb. 12, 2002 (HealthDayNews) -- A new treatment that uses a combination of gene therapy and a harmless antifungal drug could one day give patients and doctors an edge against colon cancer.

Using a technique known as "suicide gene" therapy, French scientists report that they substantially reduced colon cancer tumors and prevented the spread of the disease to other organs, such as the liver, in laboratory rats.

The researchers say the therapy could improve the poor odds of patients whose colon cancer has spread to the liver, lungs and abdominal cavity, without causing the brutal side effects of conventional chemotherapy.

The findings appear in the March issue of the journal Gut.

Colon cancer is diagnosed in approximately 107,300 Americans every year, and about 48,100 people die of the disease annually. The death rate from the disease has fallen over the last two decades, primarily because of earlier diagnosis and intervention. But the greatest risk factors remain a diet high in fat and low in fiber, a history of colorectal polyps, and being over the age of 50.

Surgery to remove colon cancer usually has a high degree of success if the tumor is found early in its development.

"But once it has migrated to the liver, it's a disaster," says Bernard Rossi, the senior investigator on the French team. "There is no good therapy at the moment once the metastatic process has started."

Rossi and his fellow scientists at the INSERM national research facility in Nice, injected an aggressive form of colon cancer, mixed with genetic material from Escherichia coli, a stomach bacterium, into the rats. The genetic material, or DNA, carried instructions for an enzyme called cytosine deaminase.

The disease was allowed to take hold and spread to the rodents' livers. The scientists then treated some of the rats with an antifungal drug known as 5-fluorocytosine.

The antifungal drug reacted with the enzyme to become 5-fluorouracil, or 5-FU, a chemotherapy drug commonly used to treat colon cancer. The drug attacked the colon cancer cells, shrinking the tumors by an average of 70 percent within 30 days, compared to rats that didn't receive the antifungal drug but did get the enzyme.

The chemotherapy drug also sought out and destroyed cancer cells that had spread beyond the colon. In 45 percent of the rats that received the antifungal drug, the cancer that had spread to the liver was wiped out. And it was significantly reduced in the rest of the rats.

"Even at a distance from the site of production of 5-FU, the same kind of tumor cells were [attacked] by the immune response and disappeared," says Rossi.

In addition, this genetically engineered chemotherapy drug did not cause the side effects that normally go hand-in-hand with anti-cancer drugs, the researchers say.

Dr. Ronald Crystal, director of the Institute for Genetic Medicine at Cornell University's Weill Medical College in New York City, says it's the lack of side effects that makes the French researchers' approach appealing.

"You get high local concentrations of a drug that may be able to be lethal to the cancer, but you don't have, theoretically, the kinds of side effects that you have with giving systemic chemotherapy," he says.

But although the theory is promising, and the animal studies have been generally successful, Crystal points out that human cancers are somewhat different.

"The real question is whether you can get it to work in a human, and you don't know that until you do a human study," he says.

The French researchers are trying to arrange a human trial of the therapy. "This could be a very exciting alternative to treat liver metastasis of colon cancer," says Rossi.

What To Do: For more information on colon cancer, visit the Web sites for the American Cancer Society, the National Cancer Institute, or the Colon Cancer Alliance.

SOURCES: Interviews with Bernard Rossi, Ph.D., director, INSERM Unit, Nice, France; Ronald G. Crystal, M.D., director, Institute for Genetic Medicine, Weill Medical College, Cornell University, New York City; March 2002 Gut
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