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Transplant Drug Reduces Risk of Cancer

Rapamycin blocks blood vessel growth to mouse tumors, study shows

FRIDAY, Feb. 1, 2002 (HealthDayNews) -- An organ transplant patient's risk of cancer after surgery may hinge on which anti-rejection drug he or she receives, says new research.

Scientists report mice with colon cancer that received the immune-suppressing drug rapamycin -- also known as sirolimus or Rapamune -- were less likely to have the cancer spread to their liver.

A transplantation expert says the findings, which appear in the February issue of Nature Medicine, could be applied to humans very soon.

Nearly 23,000 Americans have organ transplants every year, and patients may need to take immune-suppressing drugs for years to prevent rejection of a new organ.

Despite the obvious benefit of these drugs, they come with many side effects, including weight gain, nausea and difficulty sleeping. More serious, however, is that because the drugs suppress the body's immune system, patients can face a 20-fold to 500-fold higher incidence of certain cancers.

Now, researchers at the University of Regensburg in Germany have shown that mice with colon cancer that were treated with rapamycin showed dramatically lower tumor growth than similar animals treated with cyclosporine, an older immunosuppressive drug.

The rapamycin-treated mice showed less evidence of new blood vessel growth to supply any spreading cancer compared to the cyclosporine-treated mice, where the older drug appeared to promote the early stages of blood vessel formation. Eleven days after the animals began treatment, the mice in the cyclosporine group had an advanced vascular network, while rapamycin had inhibited blood vessel growth.

Senior investigator Edward K. Geissler, a professor of experimental surgery, says the drug appears to inhibit the growth of endothelial cells that make up new blood vessels leading to tumors, although exactly what it does is still not clear.

Further testing found cyclosporine increased levels of vascular endothelial growth factor (VEGF), a crucial element in angiogenesis, while rapamycin reduced but did not block the compound.

Finally, the researchers tested the effects of rapamycin on tumors in mice. Untreated animals with the tumors died within two weeks, but tumor growth in mice that received low doses of rapamycin slowed during the first 20 days of treatment. These doses matched levels normally used in immunosuppressive therapy. The tumors then started to shrink, and the mice survived. Higher doses caused faster tumor shrinkage, but the cancer then returned and killed the mice.

"Rapamycin has been approved for use, and right now there are many patients out there who've had an organ transplant that have cancer," says Geissler. "If they're on cyclosporine or conventional immunosuppression, they can remove the immunosuppression to slow the tumor growth, but then they risk [organ rejection]."

Geissler says these findings could give transplant patients who develop cancer a new option. "It should be something that can be implemented immediately," he says.

Dr. Stuart J. Knechtle, a professor of surgery at the University of Wisconsin in Madison, says the findings are important, especially for liver transplant patients whose condition is often complicated by cancer.

"We always have to worry about the risk of recurrence of that tumor," says Knechtle. "If they can be managed with an immunosuppressive agent that might reduce their risk of that tumor, that's not only novel and unique, but it's the opposite of what we currently have."

He says if researchers discover rapamycin has the same effect on humans, "it would be very exciting to have a new immunosuppressive drug that could not only help prevent rejection, but could help prevent recurrence of the tumor."

What To Do

Read about rapamycin from the University of Pittsburgh Medical Center Health System, or check out this information from the United Network for Organ Sharing on medications after a transplant.

Fifteen Americans die every day waiting for an organ transplant. Become a donor – check out the U.S. Department of Health and Human Services for details.

SOURCES: Interviews with Edward K. Geissler, Ph.D., professor, experimental surgery, Department of Surgery, University of Regensburg, Regensburg, Germany; Stuart J. Knechtle, M.D., professor, Division of Transplantation, Department of Surgery, University of Wisconsin, Madison; February 2002 Nature Medicine
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