Biology of Brain Cancer Study Points to New Drug Option
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NR-07-05 (08/03/2005). For more information, please contact Sara Harris at (202) 462-6688 or sharris@sfn.org.
BIOLOGY OF BRAIN CANCER STUDY POINTS TO NEW DRUG OPTION
WASHINGTON, DC July 20, 2005 – A drug currently approved for the treatment of Crohn’s disease may also be useful in treating the type of brain tumors called gliomas, scientists report.
A team of researchers led by Harald Sontheimer, PhD, professor of neurobiology and director of the Civitan International research center at the University of Alabama at Birmingham, found that gliomas depend on a single mechanism to protect their cells from the toxic byproducts of metabolism. Healthy cells, both in the brain and elsewhere, protect themselves through a number of different mechanisms. The researchers then showed how the mechanism can be inactivated by sulfasalazine, a drug used to treat inflammatory diseases including Crohn's, and indicate that it may stop tumor growth. The new report appears in the August 3 issue of The Journal of Neuroscience.
“This is a novel mechanism for trying to attack brain tumor cells,” says Evan Snyder, MD, PhD, stem cell and regeneration program director at the Burnham Institute in La Jolla, Calif. “Implementing their hypothesis wouldn't require designing a whole new line of drugs.”
Brain tumors kill off healthy neurons to make room for their own expansion. And they grow fast, meaning tumors have a higher rate of metabolic activity, creating and using more energy than healthy cells. Cystine is used to make a substance known as glutathione (GSH), which protects cancer cells and healthy cells alike from toxic byproducts of metabolism, so tumor cells' need for cystine is high. As the cells take up cystine to make the protective GSH, they release the neurotransmitter glutamate, which kills off neurons.
Scientists have tried to stop brain cancer by blocking the synthesis of GSH before, but Sontheimer's findings point to a new drug alternative that takes advantage of the unique biology of glioma cells, identifying the mechanism of cystine-glutamate exchange as gliomas' “Achilles' heel.”
Preliminary studies on animals have shown that drug treatments acting on this mechanism dramatically reduce tumor size, Sontheimer says. “With further successful testing, this should allow a rapid translation into clinical studies. Most exciting is the fact that a clinically approved drug that can be delivered orally is already available.”
“Brain tumors like glioblastoma annually kill 20,000 Americans,” says Jeffrey D. Rothstein, MD, PhD, director of the Robert Packard Center for ALS Research at Johns Hopkins University. “The treatment options are limited—so new research providing therapeutic approaches is very important.”
Sontheimer is a member of the Society for Neuroscience, an organization of more than 36,000 basic scientists and clinicians who study the brain and nervous system. The Society publishes The Journal. He can be reached at sontheimer@uab.edu.
