TMET-54. Rewiring of cortical glucose metabolism fuels human brain cancer growth

Abstract The brain avidly consumes glucose to fuel neurophysiology. Cancers of the brain, such as glioblastoma (GBM), relinquish physiological integrity and gain the ability to proliferate and invade healthy tissue. How brain cancers rewire glucose utilization to drive aggressive growth remains elusive. Here, we infused 13C-labeled glucose into patients and mice with brain cancer, coupled with quantitative metabolic flux analysis, to map the fates of glucose-derived carbon in tumor vs. cortex. Through the first direct and comprehensive measurements of carbon and nitrogen labeling in both cortex and glioma tissues, we uncover profound metabolic transformations. In human cortex, glucose carbons fuel essential physiologic processes including TCA cycle oxidation and neurotransmitter synthesis. Conversely, gliomas downregulate these processes and scavenge alternative carbon sources such as amino acids from the environment, repurposing glucose-derived carbons to generate molecules needed for proliferation and invasion. Targeting this metabolic rewiring in mice through dietary amino acid modulation selectively alters GBM metabolism, slows tumor growth, and augments the efficacy of standard-of-care treatments. These findings illuminate how aggressive brain tumors exploit glucose to suppress normal physiological activity in favor of malignant expansion and offer potential therapeutic strategies to enhance treatment outcomes.

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Publication Details

Journal
Neuro-Oncology
Published
2025-11-01
DOI
https://doi.org/10.1093/neuonc/noaf201.1745
Primary Topic
Cancer, Hypoxia, and Metabolism
Type
article
Field-Weighted Citation Impact
0.00
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article

TMET-54. Rewiring of cortical glucose metabolism fuels human brain cancer growth

Peter Sajjakulnukit, Jie Xu, Anjali Mittal, Kimberly Redic et al.
Neuro-Oncology
Cancer, Hypoxia, and Metabolism
article

TMET-54. Rewiring of cortical glucose metabolism fuels human brain cancer growth

Peter Sajjakulnukit, Jie Xu, Anjali Mittal, Kimberly Redic, Jann Nagina Sarkaria, Navyateja Korimerla, Andrew J. Scott, Sriram Venneti, Erina Vlashi, Ningning Liang, Krithika Suresh, Deepak Nagrath, Johanna ten Hoeve, Anthony Andren, Vijay Tarnal, Theodore S. Lawrence, Angelica Lin, Daniel Wahl, Nathalie Y.R. Agar, Wajd N. Al‐Holou, Donna M. Edwards, Gerard Baquer, Sravya Palavalasa, Weihua Zhou, Zhe Wu, Alexandra O’Brien, Sylwia A. Stopka, Abhinav Achreja, Justine Bailleul, Junyoung O. Park, Michael S. Regan, Kari Wilder-Romans, Ayesha U. Kothari, Costas Andreas Lyssiotis, Ethan Yang, Nathan Qi, Baharan Meghdadi, J Fischer, Jiane Feng, Li Zhang
article en

Abstract

Abstract The brain avidly consumes glucose to fuel neurophysiology. Cancers of the brain, such as glioblastoma (GBM), relinquish physiological integrity and gain the ability to proliferate and invade healthy tissue. How brain cancers rewire glucose utilization to drive aggressive growth remains elusive. Here, we infused 13C-labeled glucose into patients and mice with brain cancer, coupled with quantitative metabolic flux analysis, to map the fates of glucose-derived carbon in tumor vs. cortex. Through the first direct and comprehensive measurements of carbon and nitrogen labeling in both cortex and glioma tissues, we uncover profound metabolic transformations. In human cortex, glucose carbons fuel essential physiologic processes including TCA cycle oxidation and neurotransmitter synthesis. Conversely, gliomas downregulate these processes and scavenge alternative carbon sources such as amino acids from the environment, repurposing glucose-derived carbons to generate molecules needed for proliferation and invasion. Targeting this metabolic rewiring in mice through dietary amino acid modulation selectively alters GBM metabolism, slows tumor growth, and augments the efficacy of standard-of-care treatments. These findings illuminate how aggressive brain tumors exploit glucose to suppress normal physiological activity in favor of malignant expansion and offer potential therapeutic strategies to enhance treatment outcomes.

Neuro-OncologyVol. 27(Supplement_5)
Mayo Clinic (US), Harvard University (US), University of California, Los Angeles (US), Bruker (United States) (US), University of Michigan (US), Mayo Clinic in Florida (US)
Openalex Percentile: Top 59%
Cancer, Hypoxia, and Metabolism
DOIOpen Access PDFOpenAlex
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