The mechanical landscape of cancer: Exploring mechanical characteristics-based therapeutic approaches

Abstract

Tumor mechanical alterations have emerged as a critical but underexplored marker of cancer. Cells within the tumor microenvironment (TME) are constantly exposed to matrix remodeling, aberrant shear stress, cytoskeletal tension, and tumor thrombi, all of which modulate tumor progression, therapy resistance, and stromal remodeling. This review summarizes recent advances in understanding how mechanical cues regulate tumor behavior through mechanotransduction pathways, and evaluates therapeutic strategies targeting extracellular matrix (ECM) stiffness, cytoskeletal contractility, ion channels, and physical interventions. While these approaches demonstrate translational promise, most studies remain descriptive, and major challenges, including off-target effects, limited drug penetration, and biomarker validation, continue to impede clinical application. We highlight the emerging concept of “tumor mechanomics”, which integrates biomechanical fingerprints with molecular and clinical data, offering a framework for developing predictive biomarkers and guiding precision oncology.