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The Keystone to Resistance after Chemotherapy for Prostate Cancer

The Keystone to Resistance after Chemotherapy for Prostate Cancer

When cancer cells are treated with chemotherapy, the Keystone cancer cells stop dividing, and seem to hibernate. Because chemotherapy kills cells that are dividing, “the Keystone cancer cells survive.”

Consider, if you will, the Monterey Pine tree. Its cones only open after a fire reaches a certain temperature. Its whole survival has adapted so that after a wildfire, it will release many seeds at once to repopulate the burnt forest.

Brady scientists Sarah Amend, Ph.D., and Ken Pienta, M.D., the Donald S. Coffey Professor of Urology, have found that something similar happens in prostate cancer cells in response to the stress of chemotherapy. “Using an imaging system that allows us to track cells over time, we observed prostate cancer cells responding to chemotherapy stress,” says Amend. “We found, existing within the larger cancer cell population, a distinctive rare cell subtype,” which they have named the Keystone cancer cell. These Keystone cancer cells are giant and have extra DNA as compared to the other cancer cells. “These cells have been observed by scientists for a century, but have long been dismissed as insignificant, thought to be artifacts or dying cells,” adds Pienta.

They seem to be just the opposite: Amend and Pienta have discovered that these cells – like the Monterey pine cone seeds after fire – “emerge under therapeutic stress,” says Amend. “Based on our recent observations, where we observed them as live, functioning cells, we now believe Keystone cells are critical operators of resistance.” They found that when cancer cells are treated with chemotherapy, the Keystone cancer cells stop dividing and seem to hibernate. Because chemotherapy kills cells that are dividing, “the Keystone cancer cells survive.”

After the stress of treatment subsides, the Keystone cancer cells wake up, start dividing again, “and give rise to a generation of now-resistant daughter cells,” Amend continues. “We believe that these Keystone cancer cells are critical to therapy resistance and disease recurrence, and unless they are eliminated, cancer is going to come back after chemotherapy.” Amend and Pienta are now working to learn more about how these Keystone cancer cells are formed, “so we can learn how to target them, to make treatment for advanced prostate cancer much more effective.” Amend and her colleagues have received an award from The Patrick C. Walsh Prostate Cancer Research Fund to build on this work. 

Learn more about the next steps for this project

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