Killing Cancer Stem Cells

A new screening method identifies drugs that selectively target these elusive cells in tumors.

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.

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.

Jeffrey Rosen, a breast cancer researcher at Baylor College of Medicine, in Houston, TX, says that the study is an early example of a promising new turn in the hunt for cancer therapies. "It's very exciting that some groups are starting not to view tumors as homogeneous entities but to target subpopulations of cells we think are import for drug resistance," he says. However, Rosen notes that the results in mice were not as promising as the drug's performance in cells. He says that the cancer field is hampered by a lack of good animal models to determine which drugs will be relevant for therapies. The problem, he says, is "once you pull out a compound or drug, then how do you actually go the next step and show that it's really going to work?"

Weinberg calls the study "the first step in the direction of trying to eliminate these cells in tumors." He believes that even if the role of cancer stem cells in different kinds of cancer has not been resolved, "we have no doubt that getting rid of them is going to be an important part of creating cures."

Although this study focused on breast cancer, the researchers anticipate that the screen could be applied to any kind of epithelial cancer. Gupta says that while targeting cancer stem cells may not necessarily be a "magic bullet" in cancer treatment, "if you have a certain subpopulation of cancer cells that are resistant to standard treatment, you would want to find a compound that targets these cells." He adds that a drug that targets cancer stem cells could be used in combination with standard treatments to ensure that resistant cells are not left behind.

After some initial testing of several compounds, the researchers focused on one drug called salinomycin. They compared it to the actions of a drug commonly given in breast cancer chemotherapy, paclitaxel (also known by its brand name, Taxol), in cultured cells and in mice. While paclitaxel treatment leads to a higher proportion of drug-resistant cancer stem cells, salinomycin had the opposite effect, reducing the number of breast cancer stem cells in cultured cells more than 100 times more effectively than paclitaxel. The drug also reduced breast tumor growth in mice, although the reduction was less dramatic.

http://www.technologyreview.com/biomedicine/23222/page1/