Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Nat Methods. 2022 Sep;19(9):1048-1063. doi: 10.1038/s41592-022-01572-6. Epub 2022 Aug 25.
Characterizing metabolism in cancer is crucial for understanding tumor biology and for developing potential therapies. Although most metabolic investigations analyze averaged metabolite levels from all cell compartments, subcellular metabolomics can provide more detailed insight into the biochemical processes associated with the disease. Methodological limitations have historically prevented the wider application of subcellular metabolomics in cancer research. Recently, however, ways to distinguish and identify metabolic pathways within organelles have been developed, including state-of-the-art methods to monitor metabolism in situ (such as mass spectrometry-based imaging, Raman spectroscopy and fluorescence microscopy), to isolate key organelles via new approaches and to use tailored isotope-tracing strategies. Herein, we examine the advantages and limitations of these developments and look to the future of this field of research.
阐明癌症中的代谢对于理解肿瘤生物学和开发潜在疗法至关重要。尽管大多数代谢研究分析的是所有细胞区室的平均代谢物水平,但亚细胞代谢组学可以更详细地了解与疾病相关的生化过程。历史上,方法学上的限制阻碍了亚细胞代谢组学在癌症研究中的广泛应用。然而,最近已经开发出了区分和鉴定细胞器内代谢途径的方法,包括用于原位监测代谢的最先进方法(如基于质谱的成像、拉曼光谱和荧光显微镜)、通过新方法分离关键细胞器以及使用定制的同位素示踪策略。在此,我们研究了这些进展的优缺点,并展望了该研究领域的未来。