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.

除了许多公认的生物畸变外，实体瘤还会产生异常的物理微环境，从而促进癌症进展并赋予治疗耐药性。机械力在一系列生物大小和时间尺度上影响肿瘤，从分子水平上涉及其感知和传递的快速事件，到较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。由于在生物系统中研究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触发的影响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新兴和不同的作用，并为理解实体应力力学生物学提供了一个全面的框架。我们首先回顾了机械力，尤其是压应力的生理重要性，并讨论了它们的定义特征、生物学背景和相对大小。然后，我们解释了肿瘤中异常压应力是如何出现的，并描述了研究这些机械诱导过程的实验挑战。最后，我们讨论了减轻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。