Matrix biophysical cues drive transient or prolonged breast cancer dormancy programmes

In inert 3D matrices, matrix stiffness steers breast cancer dormancy fate: soft GelMA activates SOX9-linked transient stem-like dormancy, while stiff matrices induce NR2F1-associated prolonged dormancy.

• Why it matters: Dormant disseminated cancer cells can later reawaken, and although ECM biophysics influences this process, how stiffness specifically programs dormancy and therapy response is unclear.
• What they did: The study engineered stiffness-matched GelMA and alginate 3D matrices to separate stiffness from adhesion and degradability, then used deep learning 3D segmentation to quantify dormancy states and markers.
• The result: Transiently dormant cells from soft inert matrices retained dormancy memory and failed to form tumours in chicken chorioallantoic membranes, and patient-derived cells in soft inert matrices showed transient dormancy with therapy resistance.

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