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Experimental Drug Shrinks Breast Tumors

New Drug Wipes Out Cancer Stem Cells That Fuel Tumor Growth

Medically Reviewed by Brunilda Nazario, MD on December 11, 2009
From the WebMD Archives

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.

The chemo attacks the ordinary tumor cells, and the experimental compound goes after the breast cancer stem cells, Chang explains.

This study was funded by Merck & Co. which makes the experimental GSI used in the study.

Osborne says that Baylor researchers are also testing a Notch inhibitor in people with leukemia. "In the first patient, we saw a dramatic decrease in cancer stem cells. Then after two to three months, as the mother cells were depleted, the patient began to get better," he says.

William Gradishar, MD, a breast cancer expert at Northwestern University, tells WebMD that while current therapies shrink advanced tumors, they eventually start growing again.

"That's because they are not targeting these cancer stem cells. So this appears to be an effective approach," he says.

The next step is larger studies pitting the combination treatment against standard treatment in women with advanced breast cancer, Chang says.

Eventually the researchers hope to test the treatment to women with early-stage breast cancer, where there is better chance of a cure, she adds.

Other Breast Cancer Drugs in Pipeline

At the meeting, Gradishar reported that adding the cancer drug Nexavar to standard chemotherapy extends the time until advanced breast cancer progresses.

In the study of 220 women, tumors shrank in two-thirds of those treated with the Nexavar plus Taxol compared with about half of those treated with Taxol alone.

Also, women given the combination therapy were stable for an average of 8 months vs. 5.6 months for those treated with chemo alone.

Nexavar attacks tumors on multiple fronts, starving them of their blood supply, interfering with cell signaling that spurs tumor growth, and preventing cell division. It's already approved to treat liver and kidney cancers.

Nexavar "may provide added benefit over what you might expect with chemotherapy alone," Gradishar tells WebMD. The study was funded by Bayer and Onyx, which make and distribute Nexavar.

In a third study presented here, researchers reported that a higher dose of the anti-estrogen drug Faslodex works better than the standard dose in postmenopausal patients with advanced breast cancer.

Importantly, women given the higher dose did not experience more side effects than those given the standard dose, says Angelo Di Leo, MD, PhD, of the Hospital of Prato, in Italy.

Astra Zeneca, maker of Faslodex, funded the work.

Show Sources

SOURCES:

32nd Annual San Antonio Breast Cancer Symposium, San Antonio, Dec. 9-13, 2009.

Jenny Chang, MD, medical director, Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston.

Ken Osborne, MD, president, SABCS; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston.

William Gradishar, MD, professor of medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago.

Angelo Di Leo, MD, PhD, director, department of oncology, Hospital of Prato, Italy.

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