Discovery makes brain tumor cells more responsive to radiation

December 2, 2009,

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 , Wang said. Hundreds of cancer stem cells can quickly become a million .

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 .

"In our study, gamma-secretase inhibitors alone only moderately 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 combined with radiation at clinically relevant doses, the combination caused massive cell death in the tumors and significantly reduced survival of glioma stem cells. These findings often correlate with better tumor control."

Wang said ongoing clinical trials are testing gamma-secretase inhibitors as stand-alone therapy for breast and brain tumors. "Our study suggests that Notch inhibition using these drugs would provide significant therapeutic benefits if combined with radiotherapy, and I hope that future research will study this combination therapy in this vulnerable patient population," Wang said. "More effective radiation may be attainable if we can stop Notch signaling in the tumor ."

Source: Duke University Medical Center (news : web)

Related Stories

Recommended for you

Study tracks evolutionary transition to destructive cancer

February 23, 2018
Evolution describes how all living forms cope with challenges in their environment, as they struggle to persevere against formidable odds. Mutation and selective pressure—cornerstones of Darwin's theory—are the means ...

Researchers use a molecular Trojan horse to deliver chemotherapeutic drug to cancer cells

February 23, 2018
A research team at the University of California, Riverside has discovered a way for chemotherapy drug paclitaxel to target migrating, or circulating, cancer cells, which are responsible for the development of tumor metastases.

Lab-grown 'mini tumours' could personalise cancer treatment

February 23, 2018
Testing cancer drugs on miniature replicas of a patient's tumour could help doctors tailor treatment, according to new research.

An under-the-radar immune cell shows potential in fight against cancer

February 23, 2018
One of the rarest of immune cells, unknown to scientists a decade ago, might prove to be a potent weapon in stopping cancer from spreading in the body, according to new research from the University of British Columbia.

Putting black skin cancer to sleep—for good

February 22, 2018
An international research team has succeeded in stopping the growth of malignant melanoma by reactivating a protective mechanism that prevents tumor cells from dividing. The team used chemical agents to block the enzymes ...

Cancer risk associated with key epigenetic changes occurring through normal aging process

February 22, 2018
Some scientists have hypothesized that tumor-promoting changes in cells during cancer development—particularly an epigenetic change involving DNA methylation—arise from rogue cells escaping a natural cell deterioration ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.