July 24, 2008
Science Daily

Unraveling Brain Tumors - Molecular Biologists Devise Strategy To Starve Brain Tumors

Brain tumor researchers have found that brain tumors arise from cancer stem cells living within tiny protective areas formed by blood vessels in the brain. Killing those cells is a promising strategy to eliminate tumors and prevents them from re-growing. The researchers have found that drugs that block new blood vessel formation can destroy the protected areas and stop cancer from developing.

Brain tumors are often deadly. Figuring out a way to wipe them out has been a mystery for scientists. But now, a new discovery may offer clues and hope for those with even the most hard-to-treat tumors.

In the last two months, Will Pappas has had three surgeries, chemo and radiation.

"You hold out hope that well, it's just something little, and they can get it all. And then it wasn't. Then you think, well, at least it's not cancerous, and then it is," Cayce Pappas, Will's mom, says.

"It" is a brain tumor -- the stubborn kind that's hard to treat. In fact, doctors gave this seven-year-old only a 20 percent chance of surviving. Stories like Will's have molecular biologists determined to find a way to destroy brain tumors.

"It's what makes us all come to work in the morning," Richard Gilbertson, a molecular biologist from St. Jude Children's Hospital, says.

For years, researchers thought all cells inside a tumor were the same. But recently, they've discovered something different -- a small group of cancer stem cells.

"They give rise to all the cells that make up the cancer," Dr. Gilbertson explains.

Dr. Gilbertson's research shows those cancer stem cells live close to blood vessels, which fuel them. In lab experiments, he's proven drugs that target the blood vessels also destroy the cancer stem cells and can ultimately wipe out the tumor.

"So, if you can target those cells, you can have a devastating effect on the disease," Dr. Gilbertson says. Drugs like Avastin and Tarceva are now being tested in humans to see if they can target the cancer stem cells. "It's this tangible way of actually getting at the heart of the disease," Dr. Gilbertson says.

Will is taking the drug Tarceva. His mom is hoping it will work a miracle.

"That would be amazing. We would jump at the opportunity to increase our odds. He's still got a lot left to do," Cayce says.

Dr. Gilbertson says other cancers, like those of the blood, breast and colon, also contain cancer stem cells and maybe treated in a similar way in the future.

BACKGROUND: Researchers at St. Jude Children's Hospital have found that brain tumors appear to arise from cancer stem cells that live inside tiny protective 'niches' formed by blood vessels in the brain. Breaking down these niches is a promising strategy for eliminating the tumors and preventing them from regrowing.

ABOUT CANCER STEM CELLS: Scientists previously believed that tumors are lumps of cancerous tissue that must be completely removed or destroyed to cure a patient. But over the last five years, cancer researchers have learned that not all cancer cells are created equal. In the same way that normal tissue in the body is generated from stem cells, so is cancer. CSCs are the ultimate source of the tumor, consistently supplying it with new cells. Researchers have identified the CSCs for acute myeloma leukemia, four types of brain cancer, and breast cancer. So it is possible that we need not kill all cancer cells to rid a patient of the disease. Targeting the CSCs specifically might be much more efficient.

CANCER'S ACHILLES HEEL: To find a weakness for CSCs, neurobiologists at St. Jude compared them to noncancerous neural stem cells. These neural tissue generators are concentrated in regions rich in blood vessels. The vessels are lined with endothelial cells, which secrete chemical signals that help stem cells survive. CSCs, they discovered, required similar conditions to flourish: in over 70 human brain tumors, the CSCs were frequently located close to tiny vessels called capillaries. When the researchers injected mice with a mix of stem and endothelial cells from human brain tumors, those animals sprouted larger tumors than the mice that received stem cells alone.

NEW DRUG THERAPY: The new findings from St. Jude indicates that it is possible to kill the cancer by disrupting the shielded compartments in the small capillaries of the brain where CSCs reside. Anti-angiogenic drugs, such as Avastin, block the formation of new blood vessels. In tests with mice, those same drugs cause a significant drop in cancer stem cells and slow tumor growth. Human clinical trials are currently in progress at St. Jude to determine the effectiveness of Avastin and another anti-angiogenic drug in eliminating tumors and preventing their recurrence in children with brain cancers