Targeting Quiescence in Prostate Cancer
Technical Report,15 Sep 2015,14 Sep 2019
University of Michigan Ann Arbor United States
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A major problem in prostate cancer is finding and eliminating the non-proliferating or quiescent cancer cells. This is because early in prostate cancer, a small number of cancer cells metastasize to other tissues such as the bone, where they can lay dormant for years. Most chemotherapies target actively dividing cancer cells causing primary tumor shrinkage, but leave behind quiescent cancer cells which may seed new, more aggressive and chemo-resistant cancers at a later date. Through this research project we have made several important discoveries. 1.We have discovered that PCa cells that metastasize to the bone exhibit dramatically different cell cycle characteristics from those in the liver, suggesting signals from the bone are key to regulating PCa cell cycle and dormancy. 2. We have identified gene expression programs active during dormancy and suppressed during tumor recurrence both in the tumor itself and in the marrow environment. 3. We have generated PCa cell lines that can be sorted based upon a cell cycle reporter for quiescence and identified cell surface molecules that can be used to isolate and quantify dormant cancer cells. 4. We have performed experiments to discern how PCa quiescence modulates the effect of chemotherapies on tumor recurrence.
- Medicine and Medical Research