Targeting Extracellular Matrix Mechanobiology to Suppress Solid Tumor Progression

Solid tumor progression is associated with several mechanical changes, including compression inside the tumor and stiffening and tension at the tumor edge and in the tumor-adjacent stroma. Mechanical remodeling of the extracellular matrix is an active driver of therapeutic resistance and metastatic potential. As such, the field of mechanobiology has increasingly investigated the clinical targeting of stromal mechanics and the mechanotransduction signaling pathways activated by such stromal aberrations. Here, we review therapeutic strategies that target tumor mechanics, organized into therapies that target the matrix composition and therapies that target the downstream cellular machinery through which mechanical signals are transduced into malignant behavior. We emphasize active and past clinical trials wherever possible, recognizing that the distance between preclinical promise and clinical reality remains a central challenge in medicine. Together, these approaches highlight emerging opportunities and persistent challenges in therapeutically targeting tumor mechanics alongside traditional therapies to improve clinical cancer outcomes.