Brain tumor cells ready to be more receptive to radiation (Dec. 03, 20009) — Duke University Medical Center researchers have figured out how stem cells in the malevolent brain cancer glioma might be better able to defend against radiation therapy. And by a medicine to obstruct a particular signaling path in these cancer stem cells, they were capable to destroy many more glioma cells with radiation in a laboratory experiment.

brain-tumorThe effort builds off former research which showed that cancer stem cells oppose the effects of radiation much better than other cancer cells.

The Duke team recognized an identified signaling trail called Notch as the likely cause for the enhanced resistance. Notch in addition operates in normal stem cells, where it is vital 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 primary report that Notch signaling in tumor tissue is associated to the malfunction 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 way an attractive drug objective. The correct drug might be able to prevent the genuine bad guys, the glioma stem cells.”

Stem cells in a cancer are the foundation of cancer cell production, Wang said. Hundreds of cancer stem cells can quickly develop into a million tumor cells.

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

“In our study, gamma-secretase inhibitors only only reasonably slowed down tumor cell growth,” said senior author Dr. Bruce Sullenger, Duke Vice Chair for Research and Joseph W. and Dorothy W. Beard Professor of Surgery. “But when we looked at these molecules united with radiation at clinically relevant doses, the combination caused massive cell death in the tumors and considerably abridged endurance of glioma stem cells. These findings often associate with improved tumor control.”

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