Leveraging cellular mechano-responsiveness for cancer therapy.

Cells sense the biophysical properties of the tumor microenvironment (TME) and adopt these signals in their development, progression, and metastatic dissemination. Recent work highlights the mechano-responsiveness of cells in tumors and the underlying mechanisms. Furthermore, approaches to mechano-modulating diverse types of cell have emerged aiming to inhibit tumor growth and metastasis. These include targeting mechanosensitive machineries in cancer cells to induce apoptosis, intervening matrix stiffening incurred by cancer-associated fibroblasts (CAFs) in both primary and metastatic tumor sites, and modulating matrix mechanics to improve immune cell therapeutic efficacy. This review is envisaged to help scientists and clinicians in cancer research to advance understanding of the cellular mechano-responsiveness in TME, and to harness these concepts for cancer mechanotherapies. The physicomechanical cues in tumors are distinct from those in normal tissues in terms of matrix properties (ligands, topology, and stiffness) and physical forces (interstitial and vascular pressure). Different types of cells (cancer cells, cancer associated fibroblasts, and immune cells) in the tumor microenvironment sense physicomechanical stimuli, and mechanotransduce and reciprocally remodel the extracellular space, dynamically shaping the tumor mechanics. The cellular mechano-responses in tumors entail stiffening of extracellular matrix and activation of mechanosensitive machineries and signaling molecules. Modulating the extracellular matrix properties and targeting mechanosensitive molecules offer novel therapeutic interventions for effective cancer treatments. [ABSTRACT FROM AUTHOR]