Clinical research framework proposal for ketogenic metabolic therapy in glioblastoma

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dc.contributor.author Duraj, Tomás
dc.contributor.authorKalamian, Miriam
dc.contributor.authorZuccoli, Giulio
dc.contributor.authorMaroon, Joseph C.
dc.contributor.authorD’Agostino, Dominic P.
dc.contributor.authorScheck, Adrienne C.
dc.contributor.authorPoff, Angela
dc.contributor.authorWinter, Sebastian F.
dc.contributor.authorHu, Jethro
dc.contributor.authorKlement, Rainer J.
dc.contributor.authorHickson, Alicia
dc.contributor.authorLee, Derek C.
dc.contributor.authorCooper, Isabella
dc.contributor.authorKofler, Barbara
dc.contributor.authorSchwartz, Kenneth A.
dc.contributor.authorPhillips, Matthew C.L.
dc.contributor.authorChamp, Colin E.
dc.contributor.authorZupec-Kania, Beth
dc.contributor.authorTan-Shalaby, Jocelyn
dc.contributor.authorSerfaty, Fabiano M.
dc.contributor.authorOmene, Egiroh
dc.contributor.authorArismendi Morillo, Gabriel J.
dc.contributor.authorKiebish, Michael
dc.contributor.authorCheng, Richard
dc.contributor.authorEl-Sakka, Ahmed M.
dc.contributor.authorPflueger, Axel
dc.contributor.authorMathews, Edward H.
dc.contributor.authorWorden, Donese
dc.contributor.authorShi, Hanping
dc.contributor.authorCincione, Raffaele Ivan
dc.contributor.authorSpinosa, Jean Pierre
dc.contributor.authorSlocum, Abdul Kadir
dc.contributor.authorIyikesici, Mehmet Salih
dc.contributor.authorYanagisawa, Atsuo
dc.contributor.authorPilkington, Geoffrey J.
dc.contributor.authorChaffee, Anthony
dc.contributor.authorAbdel-Hadi, Wafaa
dc.contributor.authorElsamman, Amr K.
dc.contributor.authorKlein, Pavel
dc.contributor.authorHagihara, Keisuke
dc.contributor.authorClemens, Zsófia
dc.contributor.authorYu, George W.
dc.contributor.authorEvangeliou, Athanasios E.
dc.contributor.authorNathan, Janak K.
dc.contributor.authorSmith, Kris
dc.contributor.authorFortin, David
dc.contributor.authorDietrich, Jorg
dc.contributor.authorMukherjee, Purna
dc.contributor.authorSeyfried, Thomas N.
dc.date.accessioned2025-02-19T11:38:53Z
dc.date.available2025-02-19T11:38:53Z
dc.date.issued2024-12
dc.date.updated2025-02-19T11:38:53Z
dc.description.abstractGlioblastoma (GBM) is the most aggressive primary brain tumor in adults, with a universally lethal prognosis despite maximal standard therapies. Here, we present a consensus treatment protocol based on the metabolic requirements of GBM cells for the two major fermentable fuels: glucose and glutamine. Glucose is a source of carbon and ATP synthesis for tumor growth through glycolysis, while glutamine provides nitrogen, carbon, and ATP synthesis through glutaminolysis. As no tumor can grow without anabolic substrates or energy, the simultaneous targeting of glycolysis and glutaminolysis is expected to reduce the proliferation of most if not all GBM cells. Ketogenic metabolic therapy (KMT) leverages diet-drug combinations that inhibit glycolysis, glutaminolysis, and growth signaling while shifting energy metabolism to therapeutic ketosis. The glucose-ketone index (GKI) is a standardized biomarker for assessing biological compliance, ideally via real-time monitoring. KMT aims to increase substrate competition and normalize the tumor microenvironment through GKI-adjusted ketogenic diets, calorie restriction, and fasting, while also targeting glycolytic and glutaminolytic flux using specific metabolic inhibitors. Non-fermentable fuels, such as ketone bodies, fatty acids, or lactate, are comparatively less efficient in supporting the long-term bioenergetic and biosynthetic demands of cancer cell proliferation. The proposed strategy may be implemented as a synergistic metabolic priming baseline in GBM as well as other tumors driven by glycolysis and glutaminolysis, regardless of their residual mitochondrial function. Suggested best practices are provided to guide future KMT research in metabolic oncology, offering a shared, evidence-driven framework for observational and interventional studies.en
dc.identifier.citationDuraj, T., Kalamian, M., Zuccoli, G., Maroon, J. C., D’Agostino, D. P., Scheck, A. C., Poff, A., Winter, S. F., Hu, J., Klement, R. J., Hickson, A., Lee, D. C., Cooper, I., Kofler, B., Schwartz, K. A., Phillips, M. C. L., Champ, C. E., Zupec-Kania, B., Tan-Shalaby, J., et al. (2024). Clinical research framework proposal for ketogenic metabolic therapy in glioblastoma. BMC Medicine, 22(1). https://doi.org/10.1186/S12916-024-03775-4
dc.identifier.doi10.1186/S12916-024-03775-4
dc.identifier.eissn1741-7015
dc.identifier.urihttp://hdl.handle.net/20.500.14454/2334
dc.language.isoeng
dc.publisherBioMed Central Ltd
dc.rights© The Author(s) 2024
dc.subject.otherCancer
dc.subject.otherGlioblastoma
dc.subject.otherGlutaminolysis
dc.subject.otherMetabolism
dc.subject.otherPrecision medicine
dc.subject.otherResearch design
dc.subject.otherWarburg Effect
dc.titleClinical research framework proposal for ketogenic metabolic therapy in glioblastomaen
dc.typejournal article
dcterms.accessRightsopen access
oaire.citation.issue1
oaire.citation.titleBMC Medicine
oaire.citation.volume22
oaire.licenseConditionhttps://creativecommons.org/licenses/by/4.0/
oaire.versionVoR
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