Mechanobiology of Drug Resistance

Tumor progression and therapeutic response are increasingly understood not only through genetic and biochemical lenses, but also through the physical and mechanical properties of the tumor microenvironment. As tissues age, extracellular matrix stiffness, cellular mechanotransduction pathways, and biomechanical signaling undergo profound remodeling — changes that can directly influence how cancer cells sense, adapt to, and respond to therapeutic intervention. Aging-associated alterations in tissue architecture, including increased matrix crosslinking, altered stromal composition, and senescent cell accumulation, create a mechanically distinct niche that may drive both cancer initiation and variable drug efficacy in older patients.Despite growing recognition that mechanical cues regulate cell fate, proliferation, and survival, the interplay between aging-related mechanobiology and drug efficacy remains poorly understood. Key open questions include how age-related changes in tissue stiffness and mechanotransduction (e.g., YAP/TAZ, integrin, and Piezo signaling) influence chemotherapy and targeted therapy efficacy; how senescent cells and the senescence-associated secretory phenotype (SASP) remodel the mechanical microenvironment to alter treatment response; and whether mechanically-informed strategies could enhance efficacy in aged or poorly-responsive tumors.This Research Topic aims to bring together mechanistic, translational, and clinical perspectives on how mechanical forces and aging biology intersect to shape drug efficacy in cancer. We welcome contributions using in vitro, organoid, animal, and patient-derived models that explore the mechanical determinants of therapy response across the lifespan.We invite submissions addressing, but not limited to, the following themes:1. Extracellular matrix stiffness and remodeling in aging tumors and drug efficacy2. Mechanotransduction pathways (YAP/TAZ, integrins, Piezo channels) in modulating therapy response3. Senescent cells, SASP, and mechanical niche remodeling in cancer treatment outcomes4. Age-related changes in tumor stroma and their impact on drug delivery and efficacy5. Biomechanical biomarkers predicting treatment response in older cancer patients6. Organoid and 3D culture models capturing age-associated mechanical cues7. Therapeutic strategies targeting mechanosensitive pathways to enhance drug efficacy8. Clinical and translational insights linking tissue mechanics, aging, and cancer outcomes Topic editors: Michelle R Dawson Source: https://www.frontiersin.org/research-topics/83985/mechanobiology-of-drug-resistance