In a quiet corner of a breast tumor, a small group of cancer cells has learned to sleep. These dormant cells, like bears hibernating through winter, can wait out chemotherapy and later wake up to cause the cancer to return. Now, scientists in the United Kingdom have found where these hidden cells live—and what keeps them safe.
Researchers at the MRC Laboratory of Medical Sciences, Imperial College London, and University College London have created the most detailed map yet of breast cancer tumors. Their study, published in the journal Genome Medicine, shows that dormant cancer cells are not scattered randomly. Instead, they cluster together in neighborhoods protected by two types of ordinary cells: immune cells called macrophages and support cells called fibroblasts. Together, these cells seem to form a shield around the sleeping cancer cells, potentially blocking chemotherapy drugs or cancer-fighting immune cells from reaching them.
"The cancer cells are really encapsulated within these areas of macrophages and fibroblasts that we think act as shields for these dormant cancer cells," said Dr. Maria Secrier, a computational biologist at UCL who co-led the research.
The team used two powerful tools to build their map. First, they used single-cell RNA sequencing, which reveals which genes each individual cell is actively using. Then they added spatial transcriptomics, which shows not just what the cells are doing, but where they sit next to each other. This combination let them see the dormant cells and their protective neighbors in unprecedented detail.
Dr. Alexis Barr, who heads the Cell Cycle Control group at the LMS, explained why these sleeping cells are so dangerous. "These cells can hide from chemotherapy and then remain in this dormant state in the tumor, and then later reactivate to drive proliferation," she said. "If we want to achieve long-term control of people's tumors and prevent tumor relapse, we have to focus on these dormant quiescent cancer cells."
One surprise finding surprised the researchers: treatment-resistant cells were already present in tumors before any treatment was given. This was true for both fast-growing aggressive tumors and slower-developing ones. Previously, scientists had assumed dormant cells were mainly a feature of slower-growing cancers. The discovery suggests that resistance may be built into the tumor's architecture from the start.
The research points toward a new way of thinking about cancer treatment. Rather than only targeting the rapidly dividing cells that make up the main tumor, doctors might one day also target the protective neighborhoods where dormant cells hide—waking them up or breaking through their shields. Secrier noted that the team still does not know whether the surrounding cells push cancer cells into dormancy, or if the cancer cells recruit and alter their neighbors. "It's very likely coming from both sides," she said.
For patients and families facing cancer, this research offers a new direction: understanding the enemy more deeply, and finding ways to prevent it from coming back.