Targeting Breast Cancer Stem Cells May Help Lower Recurrence Risk

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Breast cancer stem cells are a new target for researchers as they look for better ways to treat breast cancer. Breast cancer stem cells are sometimes called "mother" cells of a breast cancer -- they make other breast cancer stem cells and regular breast cancer cells. Breast cancer stem cells make up about 1% of all cells in a breast cancer tumor.

Research has shown that current treatments effectively destroy regular cancer cells but are not good at destroying breast cancer stem cells. Because the breast cancer stem cells survive treatment, they can still create new regular breast cancer cells to replace the ones that have been destroyed. Researchers think breast cancer stem cells' ability to survive treatment is a big part of the reason why breast cancer can come back (recur), fail to respond to treatment, or become resistant to treatment.

Very preliminary studies found that gamma secretase inhibitors, a new type of targeted therapy medicine, may weaken or destroy breast cancer stem cells. These results were presented at the 2009 San Antonio Breast Cancer Symposium.

Gamma secretase inhibitors also are known as Notch inhibitors. The Notch pathway is the mechanism that controls the number and activity of breast cancer stem cells. Researchers want to know if using Notch inhibitors in combination with traditional breast cancer treatments can improve the overall response to treatment.

In one study, researchers implanted tumor tissue containing breast cancer stem cells and regular breast cancer cells into mice. The mice then were treated with either a Notch inhibitor called MRK-003 or a placebo (sugar pill). The results suggested the Notch inhibitor weakened or destroyed the breast cancer stem cells.

New regular breast cancer cells produced by breast cancer stem cells cluster together in what's called a mammosphere. The mice treated with MRK-003 had a lower number of mammospheres compared to mice that got the placebo. Eventually the implanted tumor got smaller in mice that got MRK-003.

Because these results were promising, the researchers tested another experimental Notch inhibitor, MK-0752, in 35 women diagnosed with advanced-stage breast cancer who were being treated with Taxotere (chemical name: docetaxel). Before treatment, each cancer was biopsied and analyzed to count the number of breast cancer stem cells and mammospheres. When treatment with MK-0752 and Taxotere was completed, the cancers were biopsied and analyzed again. The researchers found that the number of breast cancer stem cells and mammospheres were considerably lower. These results suggest that the Notch inhibitor weakened or destroyed the breast cancer stem cells.

These results sound promising, but research on Notch inhibitors is just getting started. More work will help doctors figure out if Notch inhibitors could effectively and safely treat breast cancer. Research suggests that using a Notch inhibitor early on in treatment could improve overall treatment response by weakening or destroying breast cancer stem cells.

Stay tuned to Breastcancer.org for the latest news on research that can lead to new and better ways to treat breast cancer.

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