癌症中的压缩应力：表征和对肿瘤进展和治疗的影响
Compressive stresses in cancer: characterization and implications for tumour progression and treatment
影响因子:66.80000
分区:医学1区 Top / 肿瘤学1区
发表日期:2024 Nov
作者:
Julia A Linke, Lance L Munn, Rakesh K Jain
摘要
除了许多公认的生物畸变之外，实体瘤还创造了异常的物理微环境，从而为癌症进展并赋予治疗耐药性。机械力影响跨各种生物学大小和时间尺度的肿瘤，从涉及的传感和传播的分子水平的快速事件到较慢且较大的事件，包括克隆选择，表观遗传变化，细胞侵袭，转移，转移和免疫反应。由于研究这些动态刺激在生物系统中的挑战，尽管与癌症病理生理学，侵略性和治疗性抗性明显相关，但对异常升高的机械力触发的影响和途径的机理理解仍然难以捉摸。在这篇综述中，我们研究了体力在实体瘤中的出现和多种作用，并为理解固体应力机械生物学提供了全面的框架。我们首先回顾了机械力，特别是压缩应力的生理重要性，并讨论其定义特征，生物环境和相对幅度。然后，我们解释了如何在肿瘤中出现异常压缩应力，并描述研究这些机械诱导的过程的实验挑战。最后，我们讨论了减轻固体应力及其与化学疗法，放疗和免疫疗法协同作用的机械疗法的临床翻译。
Abstract
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.