Scientists identify dormant cancer cells that may drive breast cancer recurrence

Researchers from the MRC Laboratory of Medical Sciences, Imperial College London, and the UCL Genetics Institute have created a detailed cellular map of breast tumors, identifying dormant cancer cells that may survive treatment and contribute to disease recurrence.

The findings, published in Genome Medicine, show that breast tumors contain distinct regions made up of actively dividing cancer cells alongside dormant cells that temporarily stop dividing. These inactive cells can evade chemotherapy, remain hidden for months or even years, and later become reactivated, triggering tumor regrowth or cancer spread.

The researchers found that these dormant cancer cells are surrounded by immune and connective tissue cells that appear to create a protective microenvironment, shielding them from both anti-cancer therapies and the immune system.

"These cells are particularly dangerous because they can evade chemotherapy, remain dormant within the tumor, and later resume proliferation," said Dr. Alexis Barr, one of the study's senior authors and head of the Cell Cycle Control Group at the MRC Laboratory of Medical Sciences.

To investigate the tumor microenvironment, the team combined single-cell RNA sequencing with spatial transcriptomics, allowing them to identify not only which genes were active in individual cells but also where those cells were located within the tumor and how they interacted with neighboring cells.

The study also suggests that resistance to treatment may already exist within tumors before therapy begins, rather than developing solely in response to anti-cancer drugs. The researchers say this finding challenges the long-held view that cellular dormancy is mainly associated with slow-growing tumors.

Particular attention was given to the cells surrounding the dormant cancer cells. The researchers found that these regions were frequently located next to CXCL10-high macrophages and cancer-associated fibroblasts, which may form a protective barrier that prevents both immune cells and treatments from eliminating the dormant cancer cells.

"Cancer cells appear to be surrounded by zones of macrophages and fibroblasts that we believe help protect these dormant cells," said Dr. Maria Secrier of the UCL Genetics Institute.

According to the researchers, the findings could lead to new therapeutic strategies aimed at targeting both dormant cancer cells and their protective microenvironment, potentially reducing the risk of breast cancer recurrence.