Abstract | BACKGROUND: Upregulated glucose metabolism is a common feature of tumors. Glucose can be broken down by either glycolysis or the oxidative pentose phosphate pathway (oxPPP). The relative usage within tumors of these catabolic pathways remains unclear. Similarly, the extent to which tumors make biomass precursors from glucose, versus take them up from the circulation, is incompletely defined. METHODS: We explore human triple negative breast cancer (TNBC) metabolism by isotope tracing with [1,2-13C] glucose, a tracer that differentiates glycolytic versus oxPPP catabolism and reveals glucose-driven anabolism. Patients enrolled in clinical trial NCT03457779 and received IV infusion of [1,2-13C] glucose during core biopsy of their primary TNBC. Tumor samples were analyzed for metabolite labeling by liquid chromatography-mass spectrometry (LC-MS). Genomic and proteomic analyses were performed and related to observed metabolic fluxes. FINDINGS: CONCLUSIONS:
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Authors | Jonathan M Ghergurovich, Jessica D Lang, Maren K Levin, Natalia Briones, Salvatore J Facista, Claudius Mueller, Alexis J Cowan, Matthew J McBride, Esther San Roman Rodriguez, Aaron Killian, Tuoc Dao, Jeffrey Lamont, Alison Barron, Xiaoyang Su, William P D Hendricks, Virginia Espina, Daniel D Von Hoff, Joyce O'Shaughnessy, Joshua D Rabinowitz |
Journal | Med (New York, N.Y.)
(Med)
Vol. 2
Issue 6
Pg. 736-754
(06 11 2021)
ISSN: 2666-6340 [Electronic] United States |
PMID | 34223403
(Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Amino Acids
- Ribosemonophosphates
- Lactic Acid
- ribose-5-phosphate
- Glucose
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Topics |
- Amino Acids
- Carcinoma, Non-Small-Cell Lung
- Glucose
(metabolism)
- Humans
- Lactic Acid
(metabolism)
- Lung Neoplasms
- Proteomics
- Ribosemonophosphates
- Triple Negative Breast Neoplasms
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