Medical Science: Updates and Prospects Vol. 11

Cancer progression is influenced not only by genetic and biochemical changes but also by mechanical interactions within the tumour microenvironment (TME). This review summarises how extracellular matrix stiffness, shear stress, compression, interstitial fluid pressure and tissue tension regulate tumour initiation, epithelial-mesenchymal transition, circulating tumour cell survival, cancer stem cell maintenance and therapeutic resistance. Progressive tumour growth leads to severe complications, including local tissue invasion, disruption of organ function, angiogenesis, immune evasion and metastatic spread to distant organs. These complications substantially increase disease burden, reduce treatment efficacy and contribute to cancer-related morbidity and mortality. Mechanobiology examines how factors such as extracellular matrix (ECM) stiffness, shear stress, compression and tissue tension regulate tumour growth, metastasis and therapeutic resistance. Mechanical forces activate mechanotransduction pathways involving integrins, focal adhesion kinase (FAK), phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), mitogen-activated protein kinase (MAPK), and Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) signalling, thereby promoting epithelial-mesenchymal transition (EMT), cancer stemness, invasion and survival. Mechanical abnormalities also impair drug delivery and contribute to resistance to chemotherapy, radiotherapy and immunotherapy. Advanced models, including three-dimensional (3D) cultures, organoids, microfluidics and atomic force microscopy, have improved understanding of cancer mechanobiology and therapeutic targeting.