Technologies for Decoding Cancer Metabolism with Spatial Resolution.

David M Sabatini, Naama Kanarek, Walter W Chen, Michael E Pacold

Journal: Cold Spring Harbor perspectives in medicine 2025;15(7):

PMID: 39284668

Abstract

It is increasingly appreciated that cancer cells adapt their metabolic pathways to support rapid growth and proliferation as well as survival, often even under the poor nutrient conditions that characterize some tumors. Cancer cells can also rewire their metabolism to circumvent chemotherapeutics that inhibit core metabolic pathways, such as nucleotide synthesis. A critical approach to the study of cancer metabolism is metabolite profiling (metabolomics), the set of technologies, usually based on mass spectrometry, that allow for the detection and quantification of metabolites in cancer cells and their environments. Metabolomics is a burgeoning field, driven by technological innovations in mass spectrometers, as well as novel approaches to isolate cells, subcellular compartments, and rare fluids, such as the interstitial fluid of tumors. Here, we discuss three emerging metabolomic technologies: spatial metabolomics, single-cell metabolomics, and organellar metabolomics. The use of these technologies along with more established profiling methods, like single-cell transcriptomics and proteomics, is likely to underlie new discoveries and questions in cancer research.

Copyright © 2025 Cold Spring Harbor Laboratory Press; all rights reserved.

Address: Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.; Department of Radiation Oncology and Perlmutter Cancer Center, NYU Langone Health, New York, New York 10016, USA.; Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, 16610 Prague, Czech Republic.; Department of Pathology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA [email protected].; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.

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