Notch2 linked to breast cancer dormancy in bone marrow

By AI, Created 5:11 PM UTC, June 03, 2026, /AGP/ – A study in Bone Research identifies Notch2 signaling as a major driver of breast cancer cells entering dormancy in the bone marrow, where they can evade treatment for years and later trigger relapse. The findings point to new targets, including CXCR4, CD177 and stress-response pathways, that could help prevent dormant cells from reawakening.

Why it matters: - Breast cancer cells can hide in bone marrow for years and later cause relapse, even decades after treatment of the primary tumor. - The study points to Notch2 and related markers as possible targets for therapies designed to eliminate dormant cancer cells before they reactivate.

What happened: - A research team led by Professor Anna Teti at the University of L’Aquila, with collaborators at Ludwig Maximilian University of Munich and the University of Southern Denmark, identified molecular pathways tied to breast cancer dormancy in bone. - The findings were published online in Bone Research on May 14, 2026, in Volume 14. - The original paper is titled The endosteal niche regulates breast cancer cell dormancy in bone: identification of new molecular determinants.

The details: - Bone marrow niches help regulate stem cells, and the endosteal niche near the bone surface appears to shelter dormant breast cancer cells as well. - Breast cancer cells in this environment mimic some properties of healthy stem cells to survive. - Notch2, not Notch1, played the dominant role in dormancy in the experiments. - Cells with high Notch2 divided much more slowly while interacting with osteoblasts in the endosteal niche. - RNA sequencing showed lower activity in growth and division genes, alongside higher activity in genes associated with hematopoietic stem cells. - Dormant cells showed high levels of CXCR4, CD34 and TIE2, markers linked to survival in the bone marrow niche. - Cells with high CXCR4 or TIE2 formed fewer and smaller bone tumors in mice, suggesting less aggressive spread. - High Notch2 expression also activated the unfolded protein response, a stress-survival pathway. - Those cells showed elevated PERK, ATF4, CHOP and CD177, a newly identified marker linked to dormant breast cancer cells. - CD177-high cells also showed high Notch2 and CXCR4, slower proliferation and improved patient survival outcomes. - The study was supported by grants from the Italian Association for Cancer Research.

Between the lines: - The work suggests dormant cancer cells are not simply inactive; they may adopt stem cell-like survival programs that let them persist in a protected niche. - If validated further, the marker set could help identify patients who harbor dormant disease and may benefit from closer monitoring or targeted intervention.

What’s next: - The next step is translating these molecular findings into therapies that can block dormancy or force dormant cells out of hiding before they seed relapse. - The DOI for the paper is https://doi.org/10.1038/s41413-026-00535-3. - More information is available at University of L’Aquila and Bone Research on X.