Brain Tumor Action Network

October 3, 2007

Dr. John Kuo, a UW Hospital brain surgeon, knows all too well what frequently happens after he removes a cancerous tumor from a patient.

The tumor grows back, despite post-surgery radiation and chemotherapy.

Researchers have identified a new reason for such recurrences: cancer stem cells.

Like regular stem cells, lauded for their role in regulating the body and their potential to become cures for diseases, cancer stem cells can self-renew and morph into many types of cells, scientists say.

But instead of giving people a steady supply of blood, skin or vital organ tissue, they propagate cancer growth, a growing body of research suggests.

The theory, studied by Kuo and other researchers at UW-Madison and elsewhere, could explain why tumors often return after being nearly wiped out by cancer treatments.

“We’re leaving the seeds of tumors behind,” Kuo said.

He invokes warfare imagery when describing the limitations of today’s cancer therapies.

“We’re trying to attack the whole country of the enemy, but we’re missing the command and control structures,” he said.

First identified in leukemia a decade ago, cancer stem cells have since been found in brain, bone and other cancers. It’s not clear how the cells arise, but they may take shape when regular stem cells acquire certain DNA mutations, Kuo said.

If more research better defines cancer stem cells, new drugs might be developed to target and kill the cells, said Caroline Alexander, a UW-Madison researcher who studies the cells in breast cancer.

The theory also could lead to a radically new way of measuring the success of cancer therapy. Instead of assessing how much of a tumor has been destroyed, doctors might try to find out how many cancer stem cells remain.

“If this is true, it will revolutionize oncology,” Alexander said.

But much work remains to be done, she said. “It’s a good idea still waiting to be demonstrated.”

Wade Bushman, a prostate cancer surgeon and researcher at UW-Madison, also studies cancer stem cells. So does campus stem-cell scientist Gabriela Cezar.

Kuo, in his lab at UW Hospital, studies cancer stem cells in tissue donated by patients who have had brain tumor surgery.

He and other researchers chop the tumor tissue into tiny pieces. Then they bathe the pieces in the same liquid nutrients used to grow normal neural stem cells.

That encourages the cancer stem cells to grow while causing other cells in the tumor pieces to die, Kuo believes.

The result: spheres of 500 to 1,000 cells, which have a much higher concentration of cancer stem cells than the original tumors.

Kuo subjects the spheres, in glass flasks, to radiation and to chemotherapy. He does the same to other regular brain tumor cells and to healthy neural stem cells.

He’s comparing the results to see if the cancer stem cells express different genes and signals in response to the treatments. Such markers could be targets for new drugs.

“We want to know why these cells are less sensitive to radiation and chemotherapy than the tumor they came from,” he said.

The patients whose cells Kuo is studying have had malignant astrocytomas, for which the average survival after diagnosis is 14 months.

That’s what Chris Wood of Madison learned he had this summer.

After developing a tingling sensation on his left side and some difficulty grasping things with his left hand, the 49-year-old computer programmer found out he had a tumor on the right side of his brain.

Kuo operated in June, and Wood has had radiation and chemotherapy.

Wood said he was eager to donate his tissue to the bank from which Kuo gets his samples.

“I’m a huge believer in the human evolution of knowledge,” he said. “The only reason there is a chance for me today is that other people volunteered (for research) before me.”

DAVID WAHLBERG
608-252-6125

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