The physical cues of tumor microenvironment (TME) contribute greatly to the initiation and progression of cancer. Tumor tissues usually become stiffer than healthy tissues with more aligned fibers and changed porosity. In recent years, numerous studies attempted to investigate whether biophysical cues from the surrounding environment affect the biophysical, biochemical, and biological behavior of cells and consequently attribute to the development of cancer. Here, we review recent advances of our understanding of these physical cues in terms of extracellular matrix (ECM) stiffness and topography (alignment and porosity). We discuss the underlying mechanisms of changes in TME physical parameters. Then, we summarize how cancer cells sense the mechanical signals, transfer them to the downstream signaling pathways, and finally translate them to different cellular behaviors. Specifically, we discuss the role of mechanical changes of ECM in cancer cell stiffness, actin cytoskeleton organization, gene and protein expressions, the migration of cancer cells, and their response to specific treatments. We then review different methods which have been successfully utilized to model ECM physical properties. This review paper concluded with the limitations of current studies which followed by some insights into clarifying the therapeutic potential of ECM mechanical properties to target and control the development of cancer.

肿瘤微环境 (TME) 的物理线索极大地促进了癌症的发生和发展。肿瘤组织通常变得比健康组织更硬，具有更多排列的纤维和改变的孔隙率。近年来，许多研究试图调查来自周围环境的生物物理线索是否会影响细胞的生物物理、生物化学和生物行为，从而导致癌症的发展。在这里，我们回顾了我们对细胞外基质 (ECM) 刚度和地形（排列和孔隙率）方面的这些物理线索的理解的最新进展。我们讨论了 TME 物理参数变化的潜在机制。然后，我们总结了癌细胞如何感知机械信号，将它们转移到下游信号通路，并最终将它们转化为不同的细胞行为。具体而言，我们讨论了 ECM 的机械变化在癌细胞刚度、肌动蛋白细胞骨架组织、基因和蛋白质表达、癌细胞迁移及其对特定治疗的反应中的作用。然后，我们回顾了已成功用于模拟 ECM 物理特性的不同方法。这篇综述文章总结了当前研究的局限性，随后对阐明 ECM 机械特性在靶向和控制癌症发展方面的治疗潜力提出了一些见解。然后，我们回顾了已成功用于模拟 ECM 物理特性的不同方法。这篇综述文章总结了当前研究的局限性，随后对阐明 ECM 机械特性在靶向和控制癌症发展方面的治疗潜力提出了一些见解。然后，我们回顾了已成功用于模拟 ECM 物理特性的不同方法。这篇综述文章总结了当前研究的局限性，随后对阐明 ECM 机械特性在靶向和控制癌症发展方面的治疗潜力提出了一些见解。