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Experimental Drug Shrinks Breast Tumors

New Drug Wipes Out Cancer Stem Cells That Fuel Tumor Growth
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WebMD Health News

Dec. 11, 2009 (San Antonio) -- An experimental drug can slash the number of chemotherapy-resistant cancer stem cells in women with advanced breast cancer, curbing tumor growth, researchers report.

The findings are in line with the latest theory of what causes cancer, namely that cancer stem cells hiding within tumors fuel their growth. Conventional treatments fail to cure cancer, according to the theory, because they are targeting the wrong cells.

The new compound, called a gamma-secretase inhibitor or GSI, reduced the population of cancer stem cells in 35 women with advanced breast cancer, shrinking their tumors, says Jenny Chang, MD, of Baylor University in Houston.

At the San Antonio Breast Cancer Symposium (SABCS) here, Chang showed a before-and-after photo in which one could see a large breast tumor in a woman who had failed to respond to all other drugs shrinking after treatment with GSI.

Cancer Stem Cells Fuel Tumor Growth

All stem cells -- regardless of their source -- share some general properties: They can reproduce and make exact copies of themselves, they live longer than ordinary cells, and they can give rise to other cells in our bodies.

Cancer stem cells are a perversion of other adult stem cells. Chang says that fewer than 10% of breast cancer cells have stem cell properties, but that it is this small number that continually reproduce and fuel tumor growth.

"If you can get rid of the 'mother cells' so they can't have offspring, eventually the tumor will go away," Baylor University's Ken Osborne, MD, who is president of SABCS, tells WebMD.

Cancer Stem Cells Drop, Breast Tumors Shrink

In her first set of experiments, Chang took biopsies of breast tissue from dozens of women, before and after chemotherapy. The number of cancer stem cells shot up after chemo.

Then, she injected the post-chemo tissue samples into mice with compromised immune systems.  Tumors identical to those in the women rapidly formed.

Then the researchers identified a cellular pathway -- called the Notch pathway -- that regulates self-renewal of cancer stem cells.

"These breast cancer stem cells are dependent upon the Notch pathway for survival," Chang says.

Chang theorized that shutting down the Notch pathway would deplete the supplies of cancer stem cells.

So she then tested the new compound [GSI] which is known to block the Notch pathway in mice that grew human tumors. It worked. The number of cancer stem cells that would otherwise have remained dropped.

Now, Chang and colleagues are testing the drug, in combination with a commonly used chemotherapy drug, in women with advanced breast cancer. So far, 35 women have been treated in the ongoing study.

Tissue samples after treatment showed a dramatic drop in the number of stem cells. And after several rounds of treatment, tumors started to shrink, she tells WebMD.

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