Some brain tumors may contain small populations of cancer stem cells that are resistant to radiation therapy, and this may help explain why the disease often recurs after treatment, even when there are no detectable signs of cancer.

Researchers at Duke University Medical Center have found that cancer stem cells isolated from brain tumor tissues can survive radiation treatments. Although their DNA is damaged, these cells make repairs more efficiently than other tumor cells.

"We found that cancer stem cells could deal with DNA damage from both chemotherapy and radiation more readily than other cells and survive better," says lead investigator Dr. Jeremy Rich.

His team used a protein called CD133 to distinguish potential cancer stem cells from other cells in glioblastoma tumors, the most common form of brain cancer. The disease resists all treatments, and most patients survive only a year after diagnosis.

The new findings, published early online October 18 in Nature, point to a role for cancer stem cells in glioblastoma, and they add to growing evidence that these rare cells may be the critical targets for treating cancer.

Cancer stem cells were first reported in the brain in 2004. Dr. Peter Dirks of the Hospital for Sick Children in Toronto led a team that isolated brain tumor cells with some of the properties of stem cells. The cells could divide indefinitely, give rise to various types of cells, and form tumors when transplanted into mice.

The definition of a cancer stem cell has been controversial, and the Duke team did experiments to show that they were working with cancer stem cells or cells with similar properties. In one example, when a few hundred of these cells were transplanted into mice, they formed tumors that resembled the original tumors, even after being irradiated.

"This is an exciting study," says Dr. Dirks. "It's important to show that cancer stem cells are resistant to treatment because that will redouble our efforts to consider those cells as the most crucial for cancer therapy."

The study offers insights into the biology of the tumor that could be relevant to treating patients. Knowing that DNA repair was important, the researchers blocked the DNA-repair response in mice as a potential strategy for overcoming resistance.

It seemed to work - radiation treatments killed cancer stem cells in mice when drugs inhibited their "checkpoint" proteins, which regulate DNA repair.

This study provides the first evidence of a potential mechanism - enhanced DNA repair - that allows cancer stem cells in solid tumors to survive and that could be targeted by therapies, says Dr. Craig Jordan of the University of Rochester. His team has developed ways to selectively target leukemia stem cells while sparing normal cells.

"The efficacy with which the researchers could kill these cells with radiation in the presence of a checkpoint inhibitor was striking," notes Dr. Jordan. "This is proof of concept in the brain cancer field that it is possible to target malignant stem cells."

Whether the results will be clinically useful remains to be seen, but they will likely be welcomed by physicians who treat this deadly disease.

"This study is encouraging," says Dr. Paul Fisher of the Stanford Comprehensive Cancer Center. "It improves our understanding of the biology, and this is the only way we are going to move forward in treating glioblastoma."

By Edward R. Winstead