Lymphoma Research Revs Up

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Research in laboratoryMADISON - After decades of stagnation in the cure rates of lymphoma patients, researchers are optimistic about a new direction in research that offers hope for those with the disease that killed former First Lady Jacqueline Kennedy Onassis and former Democratic presidential candidate Paul Tsongas.

A Wisconsin lymphoma researcher says the study of a family of proteins, referred to as BCL2, could provide a major breakthrough.

Lymphoma is a general term referring to a group of cancers that affect the lymphatic system, which is in turn involved with the body's immune system. The cancers are broadly divided into Hodgkin lymphoma and non-Hodgkin lymphoma.

"We know that over-expression of the BCL2 family proteins is common in lymphoma patients," says Dr. Brad Kahl, associate professor of medicine at the University of Wisconsin School of Medicine and Public Health (SMPH).

"If we can use a drug to weaken the interaction of these proteins, we may be able to slow the growth of, or even kill, cancer cells," Kahl said.

Kahl, a researcher with the UW Paul P. Carbone Comprehensive Cancer Center (UWCCC) and a practicing oncologist, has opened clinical trials on two drugs designed to attack the problematic protein interaction. He was also the lead investigator of a pivotal study that led to Food and Drug Administration (FDA) approval of Bendamustine, a new chemotherapy drug which does not cause hair loss and extends remission for patients with several types of incurable lymphoma.
According to Kahl, the 1970s brought cures for some of the 35 or more known lymphomas when combination chemotherapy regimens, or "cocktails," were developed. In the 1980s and '90s, researchers tested new chemotherapy drugs to mix with those cocktails. But there was little progress in curing more patients.

About 10 years ago, doctors began using rituximab, an antibody, which sticks to the outside of lymphoma cells and tags them for destruction by the patient’s immune system. Kahl says the drug, in combination with other chemotherapy, cures 15 percent more patients, considered a quantum leap in cure rates. Now Kahl and other researchers are looking for the next breakthrough and drugs which attack the BCL-2 proteins are good candidates.

"There are several drugs in development that target specific biochemical pathways in cancer cells," says Kahl.

"But we’re finding that a biochemical pathway which becomes a problem for one patient might not be a problem for another patient. However, the BCL-2 protein pathway is a problem for a high proportion of lymphoma patients," he notes.

If the drugs are shown effective by clinical trials, Kahl said they would be tested on the different variations of lymphoma and in combination with traditional drugs.

"If the new class of drugs works, the protein inhibitors may prove effective for treatment of various forms of lymphoma."

Kahl said three drugs designed to act on BCL2 family proteins will be tested and studied at the SMPH this year.

Date Published: 04/30/2009

News tag(s):  researchcancercancer researchbrad kahl

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