Transplant Drug Aids in Fighting Cancer

Rapamycin helps chemo deliver one-two punch in mice with lymphoma

WEDNESDAY, March 17, 2004 (HealthDayNews) -- A drug that helps cancer cells die a natural death can also overcome their resistance to chemotherapy, researchers report.

Cancer cells can elude the effect of drugs used to attack tumors because they have turned off the molecular self-destruct mechanism that leads to natural cell death. That mechanism can be turned on again in a number of different tumors by rapamycin, a drug now used to help organ transplants succeed, says a report in the March 18 issue of Nature by researchers at Cold Spring Harbor Laboratory in New York.

In a laboratory study, all the mice with B-cell lymphoma, a form of blood cancer, survived when they were given rapamycin and doxorubicin, a drug often used in chemotherapy. By contrast, very few of the mice treated with either drug alone survived.

Combination chemotherapy using rapamycin won't work for all kinds of cancer, because the drug acts against one specific molecular mechanism, says study author Dr. Hans-Guido Wendel, a research fellow at the laboratory. But it is possible to find drugs that will act against other mechanisms, he says.

"We are using a specific drug to illustrate a general principle of how we can treat cancers with combination chemotherapy," Wendel says.

Two protein pathways can inactivate the natural cell death mechanism called apoptosis in lymphoma, leukemia and other cancers. One of them uses a protein designated Akt, the other a protein called P13 kinase. In the Cold Spring Harbor studies, the combined rapamycin-doxorubicin therapy killed the Akt cells but not the P13 kinase cells.

So in clinical practice, doctors could use a readily available test to learn what is going on in cells from patients with lymphoma, Wendel says.

"We can see if this tumor has the lesion," he says. "If it does, we can use combination chemotherapy with rapamycin."

Planning has begun for trials of the combined chemotherapy in human lymphoma patients, in collaboration with physicians at the University of Chicago, Wendel says.

At Memorial Sloan-Kettering Cancer Center in New York City, Dr. Eric C. Holland is also working with rapamycin, but on a different type pf cancer.

"This particular pathway is active in many cancer types," says Holland, who is an associate professor of neurosurgery and cancer biology at Memorial Sloan-Kettering. "We are interested in brain tumors."

In addition to laboratory studies with mice, "we are also doing clinical studies with analogs of this drug," Holland says. Those studies are still at an early stage, he adds.

The animal studies are also exploring several other molecular pathways that block apoptosis, he says.

"We use mice to understand how various pathways are critical in different cancers," Holland says. "That will help us to find the rules that we can follow in treating cancers."

More information

A patient's guide to cancer chemotherapy can be found at the National Cancer Institute. Get a primer on blood cancers from the Leukemia & Lymphoma Society.

SOURCES: Hans-Guido Wendel, M.D., research fellow, Cold Spring Harbor Laboratory, N.Y.; Eric C. Holland, M.D., Ph.D., associate professor, neurosurgery and cancer biology, Memorial Sloan-Kettering Cancer Center, New York City; March 18, 2004, Nature
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