Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL, USA.
Howard Hughes Medical Institute and Children's Medical Center Research Institute, UT Southwestern Medical Center, Dallas, TX, USA.
Cell Metab. 2019 Sep 3;30(3):434-446. doi: 10.1016/j.cmet.2019.08.013.
Tumors display reprogrammed metabolic activities that promote cancer progression. We currently possess a limited understanding of the processes governing tumor metabolism in vivo and of the most efficient approaches to identify metabolic vulnerabilities susceptible to therapeutic targeting. While much of the literature focuses on stereotyped, cell-autonomous pathways like glycolysis, recent work emphasizes heterogeneity and flexibility of metabolism between tumors and even within distinct regions of solid tumors. Metabolic heterogeneity is important because it influences therapeutic vulnerabilities and may predict clinical outcomes. This Review describes current concepts about metabolic regulation in tumors, focusing on processes intrinsic to cancer cells and on factors imposed upon cancer cells by the tumor microenvironment. We discuss experimental approaches to identify subtype-selective metabolic vulnerabilities in preclinical cancer models. Finally, we describe efforts to characterize metabolism in primary human tumors, which should produce new insights into metabolic heterogeneity in the context of clinically relevant microenvironments.
肿瘤表现出重新编程的代谢活性，促进癌症进展。我们目前对体内控制肿瘤代谢的过程以及识别易受治疗靶向的代谢脆弱性的最有效方法了解有限。虽然文献中的大部分内容都集中在典型的、细胞自主的途径上，如糖酵解，但最近的工作强调了代谢在肿瘤之间甚至在实体瘤的不同区域之间的异质性和灵活性。代谢异质性很重要，因为它会影响治疗的脆弱性，并可能预测临床结果。这篇综述描述了目前关于肿瘤代谢调控的概念，重点介绍了内在的癌症细胞过程和肿瘤微环境施加给癌症细胞的因素。我们讨论了用于在临床前癌症模型中识别亚型选择性代谢脆弱性的实验方法。最后，我们描述了对原发性人类肿瘤代谢进行特征描述的努力，这应该会深入了解临床相关微环境中代谢异质性的新见解。
