The immune system must be suppressed following organ transplant to prevent the body from attacking the new organ. The increased cancer risk is a known threat to organ transplant patients, and had previously been linked to inability of the suppressed immune system to eliminate cancerous cells.

The new study, conducted by researchers at Cornell University, suggests the development of cancer after organ transplantation results because cyclosporine promotes the growth and spread of cancerous cell lines, not because the weakened immune system can?t destroy cancerous cells. The Cornell researchers were the first to observe that cyclosporine stimulates production of a hormone-like substance called transforming growth factor-beta (TGF-beta), which is already known to make cancer cells act more aggressively.

"Our findings suggest immunosuppressants like cyclosporine can promote cancer progression by a direct cellular effect that is independent of its effect on the host?s immune cells . . ." the Cornell researchers wrote.

Describing the study as "provocative," University of Michigan researcher Gary J. Nabel, MD, PhD, wrote in Nature: "We do not know whether cyclosporine has a similar effect on pre-cancerous cells or whether it is involved in converting cells from a benign to a cancerous state."

Furthermore, he said the new observations do not suggest the need for any additional precautions regarding cyclosporine. But they do provide insight into how cancers occur following organ transplant and strategies that may be useful in treating them. Other researchers are already working to find drugs that block TGF-beta, which could be used to slow growth and spread of cancer cells. Results of the study could supply a lead in the search for new immunosuppressive drugs, he added.

Regarding patients currently taking cyclosporine, Dr. Nabel said, "It is important they realize the findings of the paper do not change any of the known risks of the drug. And they should not alter their dosages unless recommended by their physicians. The findings will point the way to a better understanding of complications caused by the drug and lead to improved treatments in the future."

Although doctors have known that cyclosporine can increase cancer growth in some patients, this side effect must be weighed against the obvious value of treating the patient?s other life-threatening conditions by organ transplantation.

If patients are on cyclosporine, they need it, though they should be aware of the study, said Ralph Vogler, MD, scientific program director for the American Cancer Society.

The primary value of the study is the mechanism [of cyclosporine action] is better understood now. Anything that helps us understand a little more about mechanisms may eventually improve the treatment of cancer in the future, Dr. Vogler said.

• Cancer Resource Center