Turning resistance into therapeutic vulnerability: Mechano-reprogramming in cancer.

Cancer mechanics is often framed as a progression from compliant normal tissue to a stiff, fibrotic tumor. Yet this tissue-level description conceals a second and therapeutically consequential feature: rigid tumors can contain mechanically soft cancer-cell states and localized compliant niches. These mechanically soft states are associated with stem-like plasticity, invasive potential and resistance to cytotoxic lymphocytes. Converting the mechanical signals that define these resistant states into therapeutic outputs may open a new direction for solid-tumor immunotherapy.