Researchers at the University’s Comprehensive Cancer Center, in collaboration with an international cohort, have developed means of identifying two states of breast cancer stem cells, giving them new clues as to how to treat patients with cancer. By distinguishing the different states, they hope to find more targeted and effective treatments for the disease, which kills over 40,000 people each year in the U.S., according to the American Cancer Society. “What we found is that the stem cells actually are like chameleons ”” that is they can exist in two different states,” said Max S. Wicha, M.D., professor of Oncology and director of the University of Michigan Comprehensive Cancer Center. In breast cancer, a small fraction of cells act as seeds of the tumor, Wicha said. Cells in this state, known as epithelial-mesenchymal transition, are dormant but can spread to other organs in the body. The process of these cells spreading is called metastasis, and studying this process has been a key component of the research findings. The previous dearth of research on the dormant cells within the process of metastasis has posed a challenge to researchers trying to find new treatment options. “As a matter of fact, in breast cancer, we sometimes have women that go out ten or 15 years and we think are cured, and then the cancer, it turns out, was hiding in the bone,” Wicha said. Moreover, the new findings show that these exact same cells have the capacity to switch states, causing them to not only look different under the microscope, but also turn on different genes in the cell. When the cells enter the mesenchymal-epithelial transition state, they can no longer invade tissues but they can grow and reproduce into malignant tumors. The tumor microenvironment enables these cells to flip back and forth between the EMT and MET-states, researchers said. While the cells’ plasticity seems to be the reason that they are able to flip between two states, the reason for the cells’ ability to switch states at any given time is unclear. “We’re very interested in studying whether things like stress that may change some of the proteins or hormones in your body may actually cause the cells to change their state and come out of dormancy,” Wicha said. While this research targets breast cancer stem cells, other research laboratories around the world have confirmed that similar stem cells are present in other forms of cancer. The center is currently in the midst of early-stage clinical trials on drugs that target EMT-state stem cells. Wicha was confident these drugs will eventually target dormant EMT-state cells in patients. “What’s been very gratifying is to be able see the research we’re doing in the laboratory now directly move into the clinic and hopefully benefit patients with cancer,” Wicha said.

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