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Discovery makes brain tumor cells more responsive to radiation
Date:12/2/2009

DURHAM, N.C. Duke University Medical Center researchers have figured out how stem cells in the malignant brain cancer glioma may be better able to resist radiation therapy. And using a drug to block a particular signaling pathway in these cancer stem cells, they were able to kill many more glioma cells with radiation in a laboratory experiment.

The work builds off earlier research which showed that cancer stem cells resist the effects of radiation much better than other cancer cells.

The Duke team identified a known signaling pathway called Notch as the probable reason for the improved resistance. Notch also operates in normal stem cells, where it is important for cell-cell communication that controls cell growth and differentiation processes. The study was published in late November by Stem Cells journal.

"This is the first report that Notch signaling in tumor tissue is related to the failure of radiation treatments," said lead author Jialiang Wang, Ph.D., a research associate in the Duke Division of Surgery Sciences and the Duke Translational Research Institute. "This makes the Notch pathway an attractive drug target. The right drug may be able to stop the real bad guys, the glioma stem cells."

Stem cells in a cancer are the source of cancer cell proliferation, Wang said. Hundreds of cancer stem cells can quickly become a million tumor cells.

The Duke researchers, in collaboration with a team led by Dr. Jeremy Rich at Cleveland Clinic, used drugs called gamma-secretase inhibitors that target a key enzyme involved in Notch signaling pathway on gliomas in a lab dish. These inhibitors are being studied by other researchers for their ability to fight tumors in which Notch is abnormally activated, such as leukemia, breast and brain tumors.

"In our study, gamma-secretase inhibitors alone only moderately slowed down tumor cell growth," said senior author Dr. Bruce Sullenger, Duke Vice Chair for Resear
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Contact: Mary Jane Gore
mary.gore@duke.edu
919-660-1309
Duke University Medical Center
Source:Eurekalert

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