Chemotherapeutic resistance: a nano-mechanical point of view

Chemotherapeutic resistance is one of the main obstacles for cancer remission. To understand how cancer cells acquire chemotherapeutic resistance, biochemical studies focusing on drug target alteration, altered cell proliferation, and reduced susceptibility to apoptosis were performed. Advances in nano-mechanobiology showed that the enhanced mechanical deformability of cancer cells accompanied by cytoskeletal alteration is a decisive factor for cancer development. Furthermore, atomic force microscopy (AFM)-based nano-mechanical studies showed that chemotherapeutic treatments reinforced the mechanical stiffness of drug-sensitive cancer cells. However, drug-resistant cancer cells did not show such mechanical responses following chemotherapeutic treatments. Interestingly, drug-resistant cancer cells are mechanically heterogeneous, with a subpopulation of resistant cells showing higher stiffness than their drug-sensitive counterparts. The signaling pathways involving Rho, vinculin, and myosin II were found to be responsible for these mechanical alterations in drug-resistant cancer cells. In the present review, we highlight the mechanical aspects of chemotherapeutic resistance, and suggest how mechanical studies can contribute to unravelling the multifaceted nature of chemotherapeutic resistance.