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Research Yields Clues to Radiation-Resistant Brain Cancer

Stem cells spur tumor recurrence, but chemotherapy may keep them at bay

WEDNESDAY, Oct. 18, 2006 (HealthDay News) -- Some people with brain cancer don't respond to radiation therapy, and now a team of U.S. researchers think they know why.

Investigators at Duke University say a small number of tumor cells, including cancer and neural stem cells, help make these tumors resistant to radiation treatment. The particular tumors they are studying are called glioblastomas -- malignant brain tumors that often recur after radiation therapy.

The report appears in the Oct. 18 online edition of Nature.

"Brain cancer is a highly lethal cancer, and one of the reasons is resistance to current therapies," said lead researcher Dr. Jeremy N. Rich, an associate professor of medicine at Duke University. "But we can now identify a small fraction of the tumor that is really driving the overall behavior of the tumor."

In experiments with human tumor cells and in a rodent model, Rich's group found that compared to other tumor cells, brain cancer stem cells are very resistant to radiation. "This is because they activate a protective response and repair the damage from radiation," Rich said.

Cancer stem cells make up 2 percent to 4 percent of the entire tumor, he said. However, they can divide to form more copies and drive tumor formation. Glioblastoma stem cells that carry a protein called CD133 are able to activate a DNA repair pathway. This makes them better able to survive DNA damage, and more resistant to radiation therapy, the researchers found.

But Rich's team also found that drugs can disrupt this protective response, causing these stem cells to become just as sensitive to radiation as other tumor cells.

"Right now we are talking about brain tumors, but a lot of this can be quickly translated to almost all cancers," Rich said. "We believe that because many cancers have these stem cells, the lessons we have learned for brain cancer are applicable to most cancers."

Rich hopes that this discovery will lead to treatments that block cancer stem cells and improve brain cancer treatment.

"Cancer is a whole lot more complex than we have ever thought, and the more we learn, the more complex it gets," Rich said. "Hopefully, we are learning more about predicting which patients are going to benefit from certain treatments and designing better treatments."

One expert said the finding is an important step in understanding cancer and how to treat it.

"This study confirms what people have been suspecting -- that there is a subpopulation of stem cells that is the mother of all evils," said Dr. Paul Graham Fisher, the Beirne Family Director of Neuro-Oncology at Stanford University.

The hope in oncology is to find the right targets for treatment and targeting cancer stem cells appears to be a new way of improving cancer therapy, Fisher said. "There is still a long way to go, but it is another step in the right direction."

Fisher believes that fighting cancer is going to require a combination of approaches. "It's not going to be a one drug or one approach," he said. "It's going to be a combination of things. As we understand the complexity of cancer, we will be able to develop better therapies."

More information

There's more on brain tumor treatment at the American Cancer Society.

SOURCES: Jeremy N. Rich, M.D., associate professor, medicine, Duke University, Durham, N.C.; Paul Graham Fisher, M.D., associate professor, neurology, pediatrics and neurosurgery and human biology and the Beirne Family Director of Neuro-Oncology, Stanford University, Calif.; Oct. 18, 2006, Nature online
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