Dormant Breast Cancer Cells Found Shielded Within Tumors

Researchers have identified hidden pockets of dormant breast cancer cells within tumors that may evade treatment and lead to relapse. These inactive cells are often surrounded by immune and connective tissue cells. This cellular shield may protect them from therapies. The findings could explain why cancer sometimes returns after initial treatment.

The study, published in *Genome Medicine*, mapped breast tumors in detail. Scientists from the Medical Research Council (MRC) Laboratory of Medical Sciences, Imperial College London, and UCL Genetics Institute collaborated on the research. They found distinct regions of rapidly dividing cancer cells and quiescent, or dormant, cells. These dormant cells can "hibernate" and reactivate later.

Dormant cancer cells pose a challenge because many chemotherapy drugs target fast-growing cells. These inactive cells do not divide quickly, making them harder to eliminate. The research suggests that future cancer treatments may need to target both actively dividing and dormant cancer cells. They may also need to address the local environments that allow these dormant cells to persist.

Dr. Alexis Barr, co-lead author and head of the Cell Cycle Control group at the MRC Laboratory of Medical Sciences, stated that quiescent cancer cells are dangerous. They can hide from chemotherapy and later reactivate to drive tumor growth. The team used single-cell ribonucleic acid (RNA) sequencing and spatial transcriptomics to create detailed tumor maps. This allowed them to identify the location and characteristics of these dormant cells and their surrounding environment.

The analysis revealed that dormant cancer cells were frequently near CXCL10-positive macrophages, a type of immune cell, and myofibroblastic cancer-associated fibroblasts, which are tumor-supporting cells. These surrounding cells might form a protective barrier. This barrier could prevent cancer-killing immune cells or treatments from reaching the inactive cancer cells effectively. The researchers observed this pattern in both aggressive and slower-developing forms of breast cancer.

Understanding these protective neighborhoods could lead to new treatment strategies. Different parts of a tumor may respond to different drugs. Targeting the complement pathway, a part of the immune system, could make dormant cell niches more vulnerable. Researchers are still investigating whether the surrounding cells actively maintain dormancy or if the cancer cells alter their surroundings. This research aims to develop more effective combination therapies for breast cancer.