Mechanical Microenvironment-Dependent Tumor Growth Intervention: Recent Advances and Translational Outlook

In recent years, increasing attention has been directed toward the mechanical microenvironment, which has become a major research focus in elucidating the mechanisms underlying tumor progression. On one hand, endogenous mechanical cues, such as matrix stiffness, fluid shear stress(FSS), and mechanical strain, have been shown to promote tumor cell malignant phenotypes, including proliferation, migration, 4 invasion, and drug resistance. These activities are primarily through mechano-transduction pathways involving integrin-FAK and YAP/TAZ. Meanwhile, mechanical microenvironment was also found to influence immune cell activity and tumor immune evasion. On the other hand, exogenous mechanical stimuli, such as magnetic fields and ultrasound, can be harnessed for therapeutic purposes by altering the tumor mechanical microenvironment in situ to enhance drug delivery or directly induce cell apoptosis. Furthermore, mechanical interventions exhibit synergistic effects when combined with conventional therapies like radiotherapy and chemotherapy, thereby amplifying antitumor efficacy. Inspired by these impressive outcomes, recent advances and mechanism of mechanical microenvironment dependent tumor growth interventions are reviewed in current work, along with outlooks of the translation challenges of this emerging strategy. As an effort to achieve precise and effective tumor control while overcoming current limitations, attempts such as multi-omics and artificial intelligence should be considered to empower personalized mechanical intervention.