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Research suggests new treatment suitable for all patients
Date:12/31/2007

enefits to patients, and newer generations are in development. The team is working to develop a drug to target a third marker (Fra-1).

GBM tumors are often resistant to current treatments, including chemotherapy and radiation therapy. The mean survival rate of patients with GBM is about 14 months and has improved only slightly over the past decades.

"Developing molecularly targeted therapies using genetically engineered bacterial toxins represents an attractive option that may improve outcomes," said Debinski.

The fact that the three markers were not found in healthy brain tissue suggests that the proteins are highly suited as targets for therapies designed to kill cancer cells and spare healthy brain tissue. In Molecular Cancer Therapeutics, the team reported success creating a drug to kill cancer cells that have high levels of EphA2. The drug, which would be delivered by catheters directly to the tumor, was created by chemically linking a protein that binds to EphA2 with a modified bacterial toxin.

In the laboratory, the treatment potently killed all of the over-expressing EphA2 cells within 48 hours. It was also effective at reducing tumors in mice. The researchers compared the treatment's potency to the drug Debinski had previously developed to target cells that express IL-13R2.

"Both were extremely effective and highly potent," said Debinski. "Some of the tumor cells responded to the IL-13 cytotoxin, some responded to EphA2-targeted cytotoxin and some responded to both. This illustrates why we need a cocktail to cover as many patients as possible."

He said this combination treatment might also apply to breast, pancreas and prostate cancers, which also have high levels of these proteins.

The third marker, Fra-1, is believed to control the malignant features of brain tumor cells, such as the development new blood vessels to "feed" the tumor.

An additional benefit of targeting the three proteins is that the drug cocktail affects
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Contact: Shannon Koontz
shkoontz@wfubmc.edu
336-716-2415
Wake Forest University Baptist Medical Center
Source:Eurekalert

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