This recent finding suggests that there is a difference between normal stem cells and cancer stem cells that can be exploited and that Notch inhibition might be successfully used to target tumor stem cells in humans.
In a new 30 patient, metastatic breast-cancer trial getting under way at University of Michigan and two other locations, so-called Notch inhibitors will be used to attack the small percentage of tumor cells that are stem cells. Notch signaling pathways send signals from a cell's surface membrane into its nucleus. Such communication activates genes that instruct the cell to make proteins that perform various tasks. The idea of inhibiting notch communications to stop the stem cells from expanding a tumor raised a concern that normal blood-forming stem cells would be inhibited as well. Reproduction of various blood stem cells is responsible for the recreation of literally billions of new, very necessary cells in each of us every day.
Dr. Ivan Maillard and colleagues at the University of Michigan Medical School found that normal blood-forming stem cells in mice survive when Notch signaling pathways are experimentally blocked. A drug developed by Merck for Alzheimer's patients will be used as a Notch inhibitor in the trial and will be followed by chemotherapy.
SC Digest Comment: The idea that cancer is driven by stem cells is controversial. If this clinical trial is successful it will be step toward proving that stem cells are involved. The question of when and how a signal is initiated along the Notch pathway brings to mind the apparently unrelated work of Bonnie Bassler at Princeton. Her ground breaking work is in the arena of cell to cell communication in bacteria. Ms. Bassler pioneered the concept of "quorum sensing," which allows bacteria to "collectively regulate gene expression and, therefore, behavior." Perhaps there is no relationship at all between her work and what happens in stem cells, but the question is an interesting one.
Read the University of Michigan announcement.
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