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Cancer metabolism: looking forward
Nature Reviews Cancer ( IF 72.5 ) Pub Date : 2021-07-16 , DOI: 10.1038/s41568-021-00378-6
Inmaculada Martínez-Reyes 1 , Navdeep S Chandel 1, 2
Affiliation  

Tumour initiation and progression requires the metabolic reprogramming of cancer cells. Cancer cells autonomously alter their flux through various metabolic pathways in order to meet the increased bioenergetic and biosynthetic demand as well as mitigate oxidative stress required for cancer cell proliferation and survival. Cancer driver mutations coupled with environmental nutrient availability control flux through these metabolic pathways. Metabolites, when aberrantly accumulated, can also promote tumorigenesis. The development and application of new technologies over the last few decades has not only revealed the heterogeneity and plasticity of tumours but also allowed us to uncover new metabolic pathways involved in supporting tumour growth. The tumour microenvironment (TME), which can be depleted of certain nutrients, forces cancer cells to adapt by inducing nutrient scavenging mechanisms to sustain cancer cell proliferation. There is growing appreciation that the metabolism of cell types other than cancer cells within the TME, including endothelial cells, fibroblasts and immune cells, can modulate tumour progression. Because metastases are a major cause of death of patients with cancer, efforts are underway to understand how metabolism is harnessed by metastatic cells. Additionally, there is a new interest in exploiting cancer genetic analysis for patient stratification and/or dietary interventions in combination with therapies that target metabolism. In this Perspective, we highlight these main themes that are currently under investigation in the context of in vivo tumour metabolism, specifically emphasizing questions that remain unanswered.



中文翻译:

癌症代谢:期待

肿瘤的发生和发展需要癌细胞的代谢重编程。癌细胞通过各种代谢途径自主改变它们的通量,以满足增加的生物能量和生物合成需求,并减轻癌细胞增殖和存活所需的氧化应激。癌症驱动基因突变与环境营养物质的可用性相结合,可控制通过这些代谢途径的通量。当代谢物异常积累时,也可以促进肿瘤发生。过去几十年新技术的发展和应用不仅揭示了肿瘤的异质性和可塑性,而且使我们能够发现支持肿瘤生长的新代谢途径。肿瘤微环境 (TME) 可能会耗尽某些营养素,通过诱导营养清除机制来维持癌细胞增殖,迫使癌细胞适应。人们越来越认识到,TME 中除癌细胞外的细胞类型(包括内皮细胞、成纤维细胞和免疫细胞)的代谢可以调节肿瘤进展。由于转移是癌症患者死亡的主要原因,因此正在努力了解转移细胞如何利用新陈代谢。此外,人们对利用癌症遗传分析进行患者分层和/或饮食干预以及针对新陈代谢的疗法产生了新的兴趣。在此观点中,我们重点介绍了目前正在研究的体内肿瘤代谢背景下的这些主要主题,特别是强调仍未得到解答的问题。

更新日期:2021-07-16
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