83 Quick summary: Collaborative European research published in May 2026 has discovered that breast cancer cells hijack the protective Notch2 signalling pathways of healthy bone marrow stem cells to enter a dormant state and evade conventional therapies for decades. By mimicking these cellular niches and activating specific stress response genes, hidden cancer cells can survive under adverse conditions before eventually reactivating to form aggressive, secondary tumours. This breakthrough holds profound implications for healthcare practice and public policy, offering a vital diagnostic and therapeutic roadmap to design targeted treatments that eliminate dormant cells before they relapse, ultimately safeguarding the long term physical health and psychological well being of breast cancer survivors. Treating breast cancer remains a major medical challenge, largely due to the ability of cancer cells to remain hidden for years before triggering a relapse, sometimes even decades after successful treatment of the primary tumour. A small number of cancer cells can spread to the bone marrow, enter a dormant state for long periods, and later reactivate, forming aggressive secondary tumours in bone and other organs. Scientists have long known that the bone marrow provides a protective site for these dormant cells, but the mechanism behind their survival has remained unclear. Now, a research team led by Professor Anna Teti from the University of L’Aquila in Italy, in collaboration with Ludwig Maximilian University of Munich and the University of Southern Denmark, has uncovered new molecular pathways that regulate breast cancer cell dormancy in bone. The findings were published in Volume 14 of Bone Research on 14th May 2026. Bone marrow contains specialised microenvironments called niches that regulate stem cell behaviour. The endosteal niche, located near the bone surface, contains bone-forming cells called osteoblasts and is known to shelter dormant cancer cells. The researchers discovered that breast cancer cells can mimic certain properties of healthy stem cells in order to survive within these protective environments. “We discovered that breast cancer cells can exploit the same protective systems that normally maintain healthy stem cells in the bone marrow,” said Professor Teti. “This allows cancer cells to remain hidden and potentially reactivate years later.” The team studied two closely related signalling proteins, Notch1 and Notch2. Although both are present in breast cancer cells, Notch2 plays the dominant role in dormancy. Using imaging methods, gene expression analysis, and laboratory experiments, the researchers found that breast cancer cells with high Notch2 levels divided much more slowly when interacting with specialised osteoblasts in the endosteal niche, a key feature of cellular dormancy. Cells with high Notch1 levels did not show the same behaviour. RNA sequencing revealed that Notch2-rich cells showed lower activity of genes involved in cell growth and division, while activating genes associated with haematopoietic stem cells. Dormant cancer cells expressed high levels of CXCR4, CD34, and TIE2, genes that help stem cells survive within the bone marrow niche, as well as PERK, ATF4, CHOP, and CD177, markers linked to stress-response pathways that support survival under adverse conditions. Cells with high CXCR4 or TIE2 levels formed fewer and smaller bone tumours in mice, suggesting reduced metastatic potential. Notably, CD177-high cells also showed high Notch2 and CXCR4 expression, reduced proliferation, and were associated with improved patient survival outcomes. “This suggests that cancer cells can acquire stem cell-like properties to evade treatment and survive in the body for very long periods,” Professor Teti remarked. Current treatments largely focus on rapidly dividing cancer cells, leaving dormant ones untouched and capable of causing late recurrence. The identification of these molecular players opens avenues for therapies that could target dormant cells directly. By understanding how Notch2 and associated pathways maintain dormancy, researchers hope to develop strategies that either eliminate hidden cells or prevent their reactivation. Experts not involved in the study have welcomed the findings as a significant step forward in understanding breast cancer metastasis. The detailed molecular characterisation, including the role of CD177, could lead to better diagnostic tools for identifying patients at higher risk of late relapse, as well as novel drugs targeting the Notch2 pathway or the unfolded protein response. Professor Teti’s team emphasised that further research is needed to translate these discoveries into clinical applications. Clinical trials exploring inhibitors of these pathways could eventually reduce the risk of secondary tumours in bone and other organs in breast cancer survivors.