除了许多已确定的生物畸变之外，实体瘤还会产生异常的物理微环境，加速癌症进展并产生治疗耐药性。机械力影响肿瘤的生物尺寸和时间尺度，从涉及其传感和传输的分子水平的快速事件，到更慢和更大规模的事件，包括克隆选择、表观遗传变化、细胞侵袭、转移和免疫反应。由于研究生物系统中这些动态刺激的挑战，尽管与癌症病理生理学、侵袭性和治疗耐药性有明显的相关性，但对异常升高的机械力引发的效应和途径的机制理解仍然难以捉摸。在这篇综述中，我们研究了物理力在实体瘤中的新兴和多样化的作用，并为理解实体应力力学生物学提供了一个全面的框架。我们首先回顾机械力（尤其是压应力）的生理重要性，并讨论它们的定义特征、生物学背景和相对大小。然后，我们解释肿瘤中如何出现异常压应力，并描述研究这些机械诱导过程的实验挑战。最后，我们讨论了缓解固体应力的机械疗法的临床转化及其与化疗、放疗和免疫疗法协同作用的潜力。© 2024。Springer Nature Limited。

Beyond their many well-established biological aberrations, solid tumours create an abnormal physical microenvironment that fuels cancer progression and confers treatment resistance. Mechanical forces impact tumours across a range of biological sizes and timescales, from rapid events at the molecular level involved in their sensing and transmission, to slower and larger-scale events, including clonal selection, epigenetic changes, cell invasion, metastasis and immune response. Owing to challenges with studying these dynamic stimuli in biological systems, the mechanistic understanding of the effects and pathways triggered by abnormally elevated mechanical forces remains elusive, despite clear correlations with cancer pathophysiology, aggressiveness and therapeutic resistance. In this Review, we examine the emerging and diverse roles of physical forces in solid tumours and provide a comprehensive framework for understanding solid stress mechanobiology. We first review the physiological importance of mechanical forces, especially compressive stresses, and discuss their defining characteristics, biological context and relative magnitudes. We then explain how abnormal compressive stresses emerge in tumours and describe the experimental challenges in investigating these mechanically induced processes. Finally, we discuss the clinical translation of mechanotherapeutics that alleviate solid stresses and their potential to synergize with chemotherapy, radiotherapy and immunotherapies.© 2024. Springer Nature Limited.