Cognet Guillaume, Muir Alexander
Ben May Department for Cancer Research, University of Chicago, Chicago, IL, USA.
Sci Adv. 2024 Oct 4;10(40):eadq7305. doi: 10.1126/sciadv.adq7305. Epub 2024 Oct 2.
Solid tumors are characterized by dysfunctional vasculature that limits perfusion and delivery of nutrients to the tumor microenvironment. Limited perfusion coupled with the high metabolic demand of growing tumors has led to the hypothesis that many tumors experience metabolic stress driven by limited availability of nutrients such as glucose, oxygen, and amino acids in the tumor. Such metabolic stress has important implications for the biology of cells in the microenvironment, affecting both disease progression and response to therapies. Recently, techniques have been developed to identify limiting nutrients and resulting metabolic stresses in solid tumors. These techniques have greatly expanded our understanding of the metabolic limitations in tumors. This review will discuss these experimental tools and the emerging picture of metabolic limitations in tumors arising from recent studies using these approaches.
实体瘤的特征是血管功能失调,这限制了肿瘤微环境的灌注和营养物质输送。有限的灌注加上生长中的肿瘤对代谢的高需求,引发了这样一种假说,即许多肿瘤经历了由肿瘤中葡萄糖、氧气和氨基酸等营养物质供应有限所驱动的代谢应激。这种代谢应激对微环境中的细胞生物学具有重要影响,既影响疾病进展,也影响对治疗的反应。最近,已经开发出了识别实体瘤中限制性营养物质和由此产生的代谢应激的技术。这些技术极大地扩展了我们对肿瘤代谢局限性的理解。本综述将讨论这些实验工具,以及使用这些方法的最新研究所呈现的肿瘤代谢局限性的新情况。