Physical oncology is an emerging paradigm which recognizes tissue mechanics, per se, as an active modulator of tumorigenesis, treatment resistance and clinical outcome, mediated by mechanosignaling pathways, matrix remodeling and physical barriers to drugs. The tumor microenvironment displays abnormal physical properties in comparison to healthy tissue which contribute to cancer progression and resistance to current treatments. Physical aberrancies comprise the chaotic organization of tumor vasculature, an increased interstitial pressure, an increased solid stress, hypoxia, an abundant extracellular matrix and a progressive stiffening of solid tumors. The physical barriers in tumors are of critical importance, as tissue mechanics compromises drug delivery, reduces immune cell infiltration and promotes disease aggressiveness. All these physical hallmarks of cancer, although not fully understood, are inspiring new anticancer strategies aiming to target and normalize the physical anomalies of solid tumors, particularly in the field of nanomedicine. Here we summarize the recent paradigm shift of physical oncology and review some of the proposed strategies using nanomaterials to tackle the tumor microenvironment and its aberrant physical properties. Nanomedicine might harness the features of the tumor microenvironment in order to improve nanoparticle and drug delivery, or propose nano-agents that can be activated on demand to achieve a tailored spatio-temporal modulation of the tumor microenvironment, reduce tumor pressure and stiffness and alleviate the resistance to current treatments.
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