In this review article, we examine the importance of low levels of oxygen (hypoxia) in cancer biology. We provide a brief description of how mammalian cells sense oxygen. The hypoxia-inducible factor (HIF) pathway is currently the best characterised oxygen-sensing system, but recent work has revealed that mammals also use an oxygen-sensing system found in plants to regulate the abundance of some proteins and peptides with an amino-terminal cysteine residue. We discuss how the HIF pathway is affected during the growth of solid tumours, which develop in microenvironments with gradients of oxygen availability. We then introduce the concept of 'pseudohypoxia', a state of constitutive, oxygen-independent HIF system activation that occurs due to oncogenic stimulation in a number of specific tumour types that are of immediate relevance to diagnostic histopathologists. We provide an overview of the different methods of quantifying tumour hypoxia, emphasising the importance of pre-analytic factors in interpreting the results of tissue-based studies. Finally, we review recent approaches to targeting hypoxia/HIF system activation for therapeutic benefit, the application of which may require knowledge of which hypoxia signalling components are being utilised by a given tumour. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

中文翻译：

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肿瘤缺氧生物学的最新进展与诊断实践和基于组织的研究有关。

在这篇综述文章中，我们研究了低氧水平（缺氧）在癌症生物学中的重要性。我们简要介绍了哺乳动物细胞如何感测氧气。缺氧诱导因子（HIF）途径是目前表征最充分的氧气传感系统，但最近的研究表明哺乳动物还使用植物中发现的氧气传感系统来调节某些带有氨基末端的蛋白质和肽的丰度半胱氨酸残基。我们讨论了在实体瘤的生长过程中如何影响HIF通路，该瘤在微环境中随着氧的利用梯度变化而发展。然后，我们介绍“假性低氧”的概念，这是一种本构状态，与氧无关的HIF系统激活是由于多种特定肿瘤类型中的致癌性刺激而发生的，这些类型的肿瘤与诊断组织病理学家有着直接的关系。我们提供了量化肿瘤缺氧的不同方法的概述，强调了预分析因子在解释基于组织的研究结果中的重要性。最后，我们回顾了针对低氧/ HIF系统激活以取得治疗益处的最新方法，其应用可能需要了解给定肿瘤正在利用哪些低氧信号传导成分。©2020作者。John Wiley＆Sons Ltd代表大不列颠及爱尔兰病理学会出版的《病理学杂志》。强调预分析因素在解释基于组织的研究结果中的重要性。最后，我们回顾了针对低氧/ HIF系统激活以取得治疗益处的最新方法，其应用可能需要了解给定肿瘤正在利用哪些低氧信号传导成分。©2020作者。John Wiley＆Sons Ltd代表大不列颠及爱尔兰病理学会出版的《病理学杂志》。强调预分析因素在解释基于组织的研究结果中的重要性。最后，我们回顾了针对低氧/ HIF系统激活以取得治疗益处的最新方法，其应用可能需要了解给定肿瘤正在利用哪些低氧信号传导成分。©2020作者。John Wiley＆Sons Ltd代表大不列颠及爱尔兰病理学会出版的《病理学杂志》。