Researchers have identified a population of dormant cancer cells within breast tumors that may be responsible for treatment resistance and eventual disease recurrence, a finding published September 26, 2025, in Nature. Teh finding offers a potential new target for therapies aimed at preventing breast cancer from returning after initial successful treatment.
These “sleeper cells,” as described by the research team at the University of California, San Francisco, appear to enter a state of quiescence, effectively hiding from conventional chemotherapy and hormone therapies. This dormancy allows them to survive treatment and later reactivate, driving metastatic spread years-even decades-after a patient’s initial diagnosis. The research impacts the approximately 287,500 women and men in the United States expected to receive a new breast cancer diagnosis in 2025, according to the American Cancer Society.
The study, led by Dr. Sofia meraj, focused on identifying unique molecular characteristics of these dormant cells. Researchers found that these cells exhibit elevated levels of a protein called CXCL12, which promotes their quiescence and protects them from immune system detection. Blocking CXCL12 signaling in laboratory models effectively awakened the sleeper cells, making them vulnerable to existing treatments.
“We’ve known for a long time that some cancer cells can remain dormant for years, only to re-emerge and cause relapse,” explained Dr.Meraj. “This research provides a crucial understanding of how these cells become dormant and, importantly, identifies a potential way to disrupt that process.”
The team utilized single-cell RNA sequencing to analyze thousands of cells from both primary tumors and metastatic sites, revealing the distinct molecular signature of the dormant population. Further experiments demonstrated that these cells were significantly more resistant to both chemotherapy and endocrine therapy compared to actively dividing cancer cells.
Future research will focus on developing targeted therapies that specifically disrupt CXCL12 signaling or other mechanisms driving dormancy. Clinical trials are anticipated to begin within the next three to five years to evaluate the efficacy of these new approaches in preventing breast cancer recurrence.The findings also suggest that similar dormant cell populations may exist in other types of cancer,opening avenues for broader examination and treatment advancement.