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Journal article
Clinical research framework proposal for ketogenic metabolic therapy in glioblastoma
BMC medicine, v 22(1), 578
05 Dec 2024
PMID: 39639257
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Glioblastoma (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.
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Details
- Title
- Clinical research framework proposal for ketogenic metabolic therapy in glioblastoma
- Creators
- Tomás DurajMiriam KalamianGiulio ZuccoliJoseph C MaroonDominic P D'AgostinoAdrienne C ScheckAngela PoffSebastian F WinterJethro HuRainer J KlementAlicia HicksonDerek C LeeIsabella CooperBarbara KoflerKenneth A SchwartzMatthew C L PhillipsColin E ChampBeth Zupec-KaniaJocelyn Tan-ShalabyFabiano M SerfatyEgiroh OmeneGabriel Arismendi-MorilloMichael KiebishRichard ChengAhmed M El-SakkaAxel PfluegerEdward H MathewsDonese WordenHanping ShiRaffaele Ivan CincioneJean Pierre SpinosaAbdul Kadir SlocumMehmet Salih IyikesiciAtsuo YanagisawaGeoffrey J PilkingtonAnthony ChaffeeWafaa Abdel-HadiAmr K ElsammanPavel KleinKeisuke HagiharaZsófia ClemensGeorge W YuAthanasios E EvangeliouJanak K NathanKris SmithDavid FortinJorg DietrichPurna MukherjeeThomas N Seyfried
- Publication Details
- BMC medicine, v 22(1), 578
- Publisher
- BMC
- Number of pages
- 49
- Grant note
- Foundation for Metabolic Cancer TherapiesClaudia Peltz Family FoundationLewis TopperJohn and Kathy Garcia FoundationKenneth Rainin FoundationCorkin Family FoundationChildren with Cancer UKBroken Science Initiative, Delaware County Special Deputies Benevolent FundBoston College Research Expense Fund
We thank the Foundation for Metabolic Cancer Therapies, The Nelson and Claudia Peltz Family Foundation, Lewis Topper, The John and Kathy Garcia Foundation, Dr. Edward Miller, Kenneth Rainin Foundation, the Corkin Family Foundation, Children with Cancer UK, the Broken Science Initiative, Delaware County Special Deputies Benevolent Fund, and the Boston College Research Expense Fund for their support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Bob Kaplan and Eric Miller for insightful discussions. Figures created with BioRender.
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Radiation Oncology (and Nuclear Medicine); Pediatrics
- Web of Science ID
- WOS:001370662100001
- Scopus ID
- 2-s2.0-85211576729
- Other Identifier
- 991021985203504721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Oncology