Mechanotherapeutic Approaches for Mechanical Manipulation of Cancer Quiescence

<p dir="ltr">Cancer cell quiescence represents a major barrier to effective chemotherapy and radiotherapy, as dormant cells evade treatment and drive subsequent relapse. The tumor microenvironment (TME) significantly influences this dormant state through its mechanical properties, but the nuanced, differential effects of specific mechanical forces remain an underexplored avenue for therapeutic intervention. This review addresses this critical gap by synthesizing evidence that cyclic mechanical stress can actively drive quiescent cancer cells out of dormancy, thereby re-sensitizing them to existing treatments. Hence is proposed a novel mechanotherapeutic approach that leverages this principle, complimenting it with the dormancy-sustaining effects of static stress. The modulation of key mechanotransduction pathways, including ERK:p38, YAP/TAZ, and PI3K/Akt/mTOR by mechanical cues, and their implications for clinical application are discussed. Ultimately, this perspective highlights the potential of precisely timed and localized cyclic mechanical interventions, either alone or in combination with static stress relief, to overcome treatment and drug resistance, and reduce the risk of cancer relapse.</p>