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"Cancer Advance Identifies Drug to Destroy Powerful Stem Cells"
Posted by Mick on the STEM board.

By Rob Waters

Aug. 14 (Bloomberg) -- Scientists said they have found a drug compound that attacks in a new way the stem cells that fuel tumor growth, opening a path to a new type of anti-cancer treatment.

The compound, salinomycin, reduced the number of cancer stem cells 100 times more than did Bristol-Myers Squibb Co.’s Taxol, a common chemotherapy medicine, according to a report published yesterday in the journal Cell.

The idea that a small group of stem cells drives tumor growth while resisting chemotherapy has been documented by researchers for more than a decade. Scientists at Massachusetts Institute of Technology and the Broad Institute bolstered the theory by showing that the proportion of stem cells in a tumor rose after treatment with standard therapy and declined dramatically with salinomycin.

“It’s exactly the opposite of standard treatment,” said Max Wicha, director of the University of Michigan Comprehensive Cancer Center. “While chemotherapy kills the bulk of cells in a tumor and leaves the cancer stem cells behind, this new treatment does the opposite -- it actually targets and kills the cancer stem cells.”

Wicha, who has developed ways of identifying cancer stem cells, wasn’t involved in yesterday’s study, which he called a “very important” finding.

“This is telling us that cancer stem cells are not going to be resistant to everything,” Wicha said. “It tells us it’s going to be possible to develop specific compounds that can target this cell population.”

New Path to Drugs

The MIT and Broad researchers will conduct further testing of salinomycin in animals to assess its potential to treat humans, said Piyush Gupta, a researcher at the Cambridge, Massachusetts-based Broad Institute and co-author of the study. While the outcome of that research is unknown, the work pinpoints a new way to find effective drugs, he said.

“We now have a method that researchers anywhere in the world can use to find agents that can kill cancer stem cells and potentially treat cancer,” Gupta said yesterday in a telephone interview.

The strategy of finding and attacking these cells results from pioneering work by John Dick, a University of Toronto scientist who in 1997 showed that certain cells in leukemia propelled the growth of new cancer cells. In 2007, he identified similar cells in colon cancer.

Stem cells, for reasons not yet known, appear to fuel the growth of several kinds of cancer including breast, lung and brain tumors, according to studies done in recent years. The cells are resistant to standard cancer therapy, so finding a way to thwart them is important, said Judy Lieberman, a professor of pediatrics at the Immune Disease Institute at Harvard Medical School.

‘These Are the Cells’

“These are the cells that are the important cells and if you don’t eliminate them, the tumors can grow back and recur,” Lieberman said yesterday in a telephone interview. “Any way you can figure out to specifically target the cancer stem cells is going to fill an important gap in the therapies we have at hand.”

Scientists at universities and biotechnology companies including Infinity Pharmaceuticals Inc. of Cambridge, Massachusetts, and Australia’s ChemGenex Pharmaceuticals Ltd. are working to develop treatments to block the stem cells. Findings released in 2007 showed that one marketed anti-cancer drug, GlaxoSmithKline’s Tykerb, reduced the number of cancer stem cells and helped eliminate the disease in some breast cancer patients.

Tumor-Initiating Cells

Research by Jenny Chang at the Baylor College of Medicine has shown that after breast-cancer patients got chemotherapy or hormone treatments, the remaining malignancy had a greater percentage of tumor-initiating cells than before.

The MIT and Broad researchers grew cancer cells from breast tumors in a way that increased the number of stem cells. They then used rapid screening techniques to test 16,000 commercially available chemical compounds. They identified 32 candidates before settling on salinomycin as the most potent.

They tested the compound in mice in two ways. First, they exposed breast cancer stem cells in laboratory dishes to salinomycin and Taxol and tallied how many cells they would need to inject in a mouse to trigger a tumor. It took many more of the salinomycin-treated cells to spur cancer, showing that the compound was inhibiting cancer development, Gupta said.

Second, they induced tumors in mice and treated them with the two drugs. While both drugs exerted “significant anti-tumor effects,” the mice treated with Taxol had a greater proportion of cancer stem cells left in the remaining tumor. Taxol enriched the population of cancer stem cells and salinomycin reduced it, Gupta said.

“We have now a systematic way to look for compounds that selectively kill cancer stem cells,” Gupta said. “We’ve taken a lot of the serendipity out of the equation.”

The research was funded partly by the National Cancer Institute.

To contact the reporter on this story: Rob Waters in San Francisco at [e-mail].

http://www.bloomberg.com/apps/news?pid=20601124&sid=aQRhuBEamXkU