|| DukeMedNews || Brain Tumors and Drug Resistance

Background: The failure of chemotherapy to stop one type of aggressive brain tumor may be linked to a deficiency in a naturally occurring “fix-it” material in the cell, according to Duke medical center researchers. In a study reported in the July 15 issue of Cancer Research, Duke cancer and biochemistry specialists found that glioblastoma multiforme (GBM) tumors that had become resistant to chemotherapy drugs showed defects in the cellular mismatch repair system, a key factor in destroying cancer cells. The findings reinforce researchers’ beliefs that mismatch repair has broad impact on human tumor cell production.

While growing human GBM tumors in mice, the researchers treated the tumors with procarbazine, a drug commonly prescribed alone or in combination with other drugs in therapy for the brain cancer. Though procarbazine is a frontline drug treatment, most patients ultimately develop resistance to it and it ceases to check tumor growth. The tumors growing on mice developed resistance to the drug after nine treatments, giving the researchers a way to study the resistance mechanism.

Suggested lead: One of the most common and aggressive types of brain tumors is resistant to chemotherapy. And researchers at Duke University Medical Center say they think they know the reason why. Melinda Stubbee reports.

In Cut 1, Dr. Friedman says they grew the GBM tumors in mice and treated them with a common chemotherapy drug. He says they were surprised and delighted to see that the mice became resistant to the drug, and that gave them a chance to study that resistance mechanism.

Cut 1…in humans…:15
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A process called mismatch repair helps correct some of the disorder that occurs when cells go through changes. Friedman says what they found is that the resistant tumor cells have a mutation in mismatch repair, and that’s what they think leads to the resistance to certain drugs. In Cut 2, Friedman talks about what the discovery could lead to.

Cut 2…likely to work…:14
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