Targeting sleeper cancer cells to improve outcomes for breast cancer survivors

For many breast cancer survivors, the journey does not end with a clear scan and the last treatment session. Instead, it enters a phase of quiet vigilance, marked by the persistent fear that the disease could return years or even decades later. Now, new research offers a potential way to confront that fear directly by identifying and eliminating the hidden “sleeper cells” that are often responsible for a relapse.

A first-of-its-kind, federally funded Phase II clinical trial has demonstrated a proof-of-concept that it is possible to identify breast cancer survivors at a higher risk of recurrence and to effectively treat these dormant tumor cells, which are known as minimal residual disease. These cells, which can lie inactive in the body for long periods, are a major reason why breast cancer can recur years or even decades after the initial treatment, yet they are not active enough to be detected by standard imaging tests used for routine follow-up. The study aimed to seize a window of opportunity to intervene while the cancer was "sleeping".  

In the trial, led by researchers at Penn Medicine, 51 breast cancer survivors who had completed their initial treatment with clear scans were screened for the presence of these dormant tumor cells in their bone marrow. For those in whom the cells were found, a new treatment regimen using existing, repurposed drugs was administered. The results showed that this approach successfully cleared the dormant cells in 80 percent of the participants. After a median follow-up of 42 months, the three-year recurrence-free survival rate was over 90 percent for patients who received a single drug, and it reached 100 percent for those who were given a combination of both study drugs.  

The drugs used in the trial were already approved by the Food and Drug Administration for other conditions but were found to work by targeting the key biological signals that allow tumor cells to remain in a dormant state, specifically autophagy and mTOR signaling. This discovery highlights that the biological makeup of a dormant cell is distinct from that of an active tumor, providing a new way to approach the challenge of recurrence.  

This proof-of-concept study demonstrates that the "sleeper phase" represents an opportunity to intervene and eradicate dormant tumor cells before they can reactivate as aggressive, metastatic disease.  Researchers are now enrolling patients in two larger, ongoing studies to confirm and expand upon these initial findings. The work points to a future where long-term cancer survivorship could involve not just passive surveillance, but a proactive strategy to eradicate disease before it has a chance to reawaken.

This article is for informational purposes only and does not constitute medical advice. The content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read in this article.

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Original Source: DeMichele, A., Clark, A.S., Shea, E. et al. Targeting dormant tumor cells to prevent recurrent breast cancer: a randomized phase 2 trial. Nat Med (2025). https://doi.org/10.1038/s41591-025-03877-3

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