文章：

压缩应力在癌症：表征和影响肿瘤进展和治疗

Compressive stresses in cancer: characterization and implications for tumour progression and treatment

原文发布日期：2024-10-10

DOI: 10.1038/s41568-024-00745-z

类型: Review Article

开放获取: 否

英文摘要：

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.

摘要翻译： 

除了许多已明确的生物学异常，实体瘤还会形成异常的物理微环境，这种环境助长了癌症进展并赋予治疗抵抗性。机械力在多种生物尺度和时间维度上影响肿瘤——从分子层面感知和传递机械力的快速事件，到包括克隆选择、表观遗传改变、细胞侵袭、转移和免疫反应等更缓慢、更宏观的事件。尽管异常升高的机械力与癌症病理生理学、侵袭性和治疗抵抗性存在明显关联，但由于在生物系统中研究这些动态刺激存在挑战，对其触发效应及作用机制的机理认知仍显不足。本综述中，我们探讨机械力在实体瘤中日益凸显的多样化作用，并建立理解实体应力机械生物学的综合框架。我们首先回顾机械力（特别是压缩应力）的生理重要性，讨论其定义特征、生物学背景和相对强度；继而阐释异常压缩应力如何在肿瘤中产生，并描述研究这些机械诱导过程的实验挑战；最后讨论缓解实体应力的机械疗法的临床转化前景，及其与化疗、放疗和免疫疗法协同作用的潜力。

原文链接：

Compressive stresses in cancer: characterization and implications for tumour progression and treatment