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Recent evidence suggests that certain cancers may persist or recur after treatment because a small population of cells, called cancer stem cells, remains behind to seed new tumors. Though scientists are not yet certain about the role cancer stem cells play in disease, evidence is accumulating that these cells are particularly resistant to chemotherapy and radiation, and can linger in the body even after treatment.

Several research groups have begun looking for substances that kill these cells. A new approach, developed by researchers at the Whitehead Institute for Biomedical Research and the Broad Institute of MIT and Harvard, makes use of high-throughput screening methods to identify chemicals that selectively target these elusive cells. In a study published today in Cell, the researchers identify one particular drug that kills breast cancer stem cells in mice. Although it is still unclear whether the drug will be useful in humans, the researchers believe their study demonstrates that it’s possible to target these cells selectively.

Because cancer stem cells, which have the ability to give rise to new tumors, may remain behind after chemotherapy and radiation treatments, finding ways to target these cells specifically may offer a way to make treatment more effective. But accessing and studying cancer stem cells has been challenging because very few are present in tumors and they are difficult to generate and maintain outside the body. Other groups have recently screened for drugs that target leukemia stem cells and brain cancer stem cells. In the Cell paper, a team led by the labs of Eric Lander at the Broad Institute and Robert Weinberg at the Whitehead Institute developed a way to generate a large number of cells that mimic naturally occurring epithelial cancer stem cells; these cells can be maintained in this state for long periods of time.

Epithelial cancers are the most common types of cancer in adults and affect the skin and inner lining of organs in the body. Using epithelial breast cancer cells, the researchers introduced a genetic change in these cells, causing them to take on the properties of mesenchymal cells, which form connective tissue in the body. Piyush Gupta, a co-author at the Broad Institute, says that for reasons not completely known, when this “epithelial-to-mesenchymal transition” is performed on breast cancer cells, it promotes the development of a large number of cells that he says are “indistinguishable from cancer stem cells.” These cells can then be grown in tiny pockets on plates and screened robotically for their response to large collections of chemicals.

The researchers used a library of 16,000 chemicals at the Broad Institute to look for compounds that killed these transformed breast cancer stem cells more effectively than they killed normal breast cancer cells. Gupta explains that since cancer stem cells are usually resistant to drugs, relatively few chemicals are effective–a mere 32 compounds were identified in the screen as preferentially treating breast cancer stem cells.

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Credit: Piyush Gupta, Kai Tao, and Charlotte Kuperwasser

Tagged: Biomedicine

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