Breast cancer can sometimes return years after treatment, even when there is no detectable evidence of disease. Now, scientists may have uncovered an important clue: hidden groups of cancer cells that enter a dormant state and appear to be surrounded by cells that could help protect them.

Researchers from the MRC Laboratory of Medical Sciences, Imperial College London, and UCL Genetics Institute created detailed maps of breast tumours, identifying distinct areas containing rapidly dividing cancer cells and others containing dormant, or 'quiescent', cells.

The findings, published in Genome Medicine, could eventually help scientists develop treatments that target cancer cells capable of surviving therapy and becoming active again.

What Are Dormant Cancer Cells?

Cancer cells do not all behave in the same way. While some multiply rapidly, others can effectively enter a resting state.

These dormant cells may be harder to eliminate because many chemotherapy drugs work by targeting cells that are actively dividing. A cancer cell that is temporarily inactive may therefore be less vulnerable to treatment.

The researchers found evidence that some cells resembling therapy-resistant cancer cells were already present in untreated tumours, suggesting that certain features linked to treatment resistance may exist before therapy begins.

The team identified these dormant cell populations in both aggressive and slower-growing types of breast cancer, challenging the idea that tumour dormancy is mainly associated with less aggressive disease.

A 'Protective Shield' Around the Cells

The researchers were particularly interested in what surrounded the dormant cancer cells.

Using single-cell RNA sequencing and spatial transcriptomics, they mapped not only individual cell types but also their locations within breast tumours.

They found that dormant cancer cells were frequently located near CXCL10-positive macrophages, a type of immune cell, and myofibroblastic cancer-associated fibroblasts, which are cells that form part of the tumour-supporting environment.

These neighbouring cells may act as a protective 'shield', potentially helping dormant cancer cells evade immune attack or treatment. However, researchers emphasised that they do not yet know exactly how this relationship works.

It is possible that the surrounding cells help push cancer cells into dormancy. Alternatively, the cancer cells could attract or alter the surrounding cells to create a more favourable environment. The researchers believe both processes could be involved.

Could This Explain Cancer Recurrence?

The discovery offers a possible explanation for one of the most difficult problems in cancer treatment: why cancer can return after an apparently successful course of therapy.

The National Cancer Institute notes that recurrence can occur when some cancer cells survive initial treatment and later begin growing again. Breast cancer can recur locally, in nearby lymph nodes, or in distant parts of the body, sometimes many years after the original treatment.

The new research suggests that dormant cells may represent one population capable of surviving within a tumour before later becoming active.

However, the study does not prove that these cells are responsible for every breast cancer recurrence. The findings are based on detailed analysis of existing tumour data, and the researchers say the proposed mechanisms still need to be tested experimentally.

Could Future Treatments Target 'Sleeping' Cells?

The findings could eventually lead to a different approach to treating breast cancer.

Instead of focusing exclusively on rapidly dividing cancer cells, future therapies could potentially combine treatments that attack actively growing tumour cells with strategies designed to eliminate or control dormant populations and their protective surroundings.

Researchers also found increased activity in the complement pathway, part of the immune system, within some dormant cell niches. This could offer another potential target for future investigation.

For now, however, these possibilities remain experimental. The study provides an important new map of how different cancer cells and their surrounding environments coexist within breast tumours.

Understanding these 'sleeping' cancer cells could ultimately help researchers develop treatments that not only shrink tumours but also reduce the chance of cancer returning years later.

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