Beyond matrix stiffness: targeting force-induced cancer drug resistance

作者：Maria Kalli, Matthew D. Poskus, Triantafyllos Stylianopoulos, Ioannis K. Zervantonakis · 发表于：Trends in cancer · 年份：2023 · DOI：10.1016/j.trecan.2023.07.006 · 被引用次数：168 · 研究领域：Cellular Mechanics and Interactions、Nanoparticle-Based Drug Delivery、Force Microscopy Techniques and Applications

During tumor progression, mechanical abnormalities in the tumor microenvironment (TME) trigger signaling pathways in cells that activate cellular programs, resulting in tumor growth and drug resistance. In this review, we describe mechanisms of action for anti-cancer therapies and mechanotransduction programs that regulate cellular processes, including cell proliferation, apoptosis, survival and phenotype switching. We discuss how the therapeutic response is impacted by the three main mechanical TME abnormalities: high extracellular matrix (ECM) composition and stiffness; interstitial fluid pressure (IFP); and elevated mechanical forces. We also review drugs that normalize these abnormalities or block mechanosensors and mechanotransduction pathways. Finally, we discuss current challenges and perspectives for the development of new strategies targeting mechanically induced drug resistance in the clinic.