The Warburg hypothesis and the emergence of the mitochondrial metabolic theory of cancer DOI Creative Commons
Thomas N. Seyfried,

Derek C. Lee,

Tomás Duraj

et al.

Journal of Bioenergetics and Biomembranes, Journal Year: 2025, Volume and Issue: unknown

Published: April 8, 2025

Abstract Otto Warburg originally proposed that cancer arose from a two-step process. The first step involved chronic insufficiency of mitochondrial oxidative phosphorylation (OxPhos), while the second protracted compensatory energy synthesis through lactic acid fermentation. His extensive findings showed oxygen consumption was lower lactate production higher in cancerous tissues than non-cancerous tissues. considered both and extracellular as accurate markers for ATP OxPhos glycolysis, respectively. Warburg’s hypothesis challenged showing remained high some cells despite elevated suggesting largely unimpaired. New information indicates neither nor are surrogates quantification cells. also did not know significant amount could come glutamine-driven substrate level glutaminolysis pathway with succinate produced end product, thus confounding linkage to origin within mitochondria. Moreover, new shows cytoplasmic lipid droplets aerobic fermentation biomarkers insufficiency. original can now be linked more complete understanding how underlies dysregulated cell growth. These address several questionable assumptions regarding allowing field advance effective therapeutic strategies less toxic metabolic management prevention cancer.

Language: Английский

EMB-driven glioblastoma multiforme progression via the MCT4/GPX3 axis: therapeutic inhibition by Ganxintriol A DOI Creative Commons
Bo Cheng, Jing Liu, Ling Gao

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 4, 2025

Embigin (EMB) is a transmembrane glycoprotein highly expressed in glioblastoma multiforme (GBM), yet its role GBM progression remains unclear. In this study, we investigate the function of intracellular EMB promoting and evaluate effect Ganxintriol A, traditional Chinese herbal extract, treatment. Bioinformatics datasets were utilized to assess expression prognostic value patients. vitro experiments such as PCR、western blot,CCK8,transwell,wound healing,clone formation flow cytometry assays conducted examine EMB's biological functions underlying mechanisms cell lines. Additionally, constructed subcutaneous tumor model nude mice evaluated medicine extract A on through vivo experiments. associated with poor prognosis overexpression accelerated progression, whereas knockdown had opposite effect. Further analysis revealed that upregulated epithelial-mesenchymal transition (EMT) glycolysis while maintaining glutathione (GSH) redox balance by inducing monocarboxylate transporter 4 (MCT4) peroxidase 3 (GPX3) expression. Treatment significantly downregulated expression, effectively inhibiting both vivo. This study highlights an independent biomarker for reveals novel mechanism which drives progression. identified promising therapeutic candidate

Language: Английский

Citations

0
Maximizing the Potential of Ketogenic Dieting as a Potent, Safe, Easy-to-Apply and Cost-Effective Anti-Cancer Therapy DOI Open Access
Simeon Ikechukwu Egba, Catherine Daniel

Archives of Cancer Science and Therapy, Journal Year: 2025, Volume and Issue: 9(1), P. 001 - 005

Published: March 3, 2025

The global menace of cancer requires supplementary treatments beyond standard medical approaches for effective intervention. Ketogenic Diet (KD) composed high fats combined with moderate proteins and low carbohydrates has become popular as a metabolic therapy cancer. anti-cancer mechanism KD works through stress induction in cells, reduced insulin IGF-1 signaling pathways, improved mitochondrial function, inflammation, immune regulation. Standard receive enhanced outcomes synergistic action which simultaneously decreases treatment-related side effects. To achieve optimized treatment cancer, ketogenic diet practitioners need to use personalized nutritional planning combination tracking exogenous ketone supplements. It is essential find solutions adherence issues nutrient deficiencies because they determine KD’s effectiveness treatment. fight against needs sustained multipronged clinical research validation establish the proper implementation this method.

Language: Английский

Citations

0
Rethinking corticosteroids use in oncology DOI Creative Commons
Pierrick Martinez, Jean‐Marc Sabatier

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: March 26, 2025

Corticosteroids (CSs), widely used in oncology for their anti-inflammatory and immunosuppressive properties, help manage cancer-related symptoms side effects. However, long-term use may negatively affect patient survival exacerbate tumor progression. Elevated glucose glutamine metabolism, disruption of vitamin D levels, alterations the microbiome are some key factors contributing to these adverse outcomes. Approaches such as ketogenic diets, fasting, sartans, supplementation have shown promise providing similar benefits CSs while mitigating risks associated with mechanisms identified This perspective underscores necessity a reevaluation cancer care advocates further research into safer, more effective therapeutic strategies.

Language: Английский

Citations

0
Therapeutic Targets in Glioblastoma: Molecular Pathways, Emerging Strategies, and Future Directions DOI Creative Commons
Justin Tang, Nishika Karbhari, Jian L. Campian

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(7), P. 494 - 494

Published: March 26, 2025

Glioblastoma (GBM) is the most aggressive primary brain tumor in adults, characterized by rapid growth, invasive infiltration into surrounding tissue, and resistance to conventional therapies. Despite advancements surgery, radiotherapy, chemotherapy, median survival remains approximately 15 months, underscoring urgent need for innovative treatments. Key considerations informing treatment development include oncogenic genetic epigenetic alterations that may dually serve as therapeutic targets facilitate resistance. Various immunotherapeutic strategies have been explored continue be refined their anti-tumor potential. Technical aspects of drug delivery blood–brain barrier (BBB) penetration addressed through novel vehicles techniques including incorporation nanotechnology. Molecular profiling has emerged an important tool individualize where applicable, identify patient populations with sensitivity. The goal this review describe spectrum potential GBM targets, provide overview key trial outcomes. Altogether, progress clinical preclinical work must critically evaluated order develop therapies strongest efficacy.

Language: Английский

Citations

0
Exploration of the multiomics-based mechanisms of Gancao Nourishing-Yin decoction in regulating mitochondrial metabolic genes CYB5R3 and PICK1 to influence glioma progression DOI Creative Commons
Yufeng Chen, Anjing Zhang, Lei Li

et al.

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 8, 2025

Glioma is the most common malignancy of central nervous system, characterised by its high invasiveness and recurrence, which significantly limit therapeutic outcomes. Energy metabolism reprogramming, especially mitochondrial dysfunction, plays a pivotal role in tumour growth, survival, progression. Mitochondria serve as hub for energy production biosynthesis, adapting through alterations oxidative phosphorylation, lipid metabolism, tricarboxylic acid cycle to meet metabolic demands gliomas. Gancao Nourishing-Yin (GCNY) decoction, traditional herbal compound, has demonstrated potential antitumour effects, particularly modulating pathways stress, are critical cell adaptation. Genomic data from glioma GWAS dataset Finnish R11 database eQTL 13 distinct brain regions were analysed using Summary-data-based Mendelian Randomization(SMR) identify glioma-associated genes. MitoCarta3.0, genes, was used pinpoint mitochondrial-related Differentially expressed genes (DEGs) human microglial cells treated with GCNY extracted GEO GSE210945 cross-referenced SMR results key Colocalisation analysis, validation TCGA database, survival functional annotations performed explore mechanisms action. Integration MitoCarta3.0 identified 19 linked gliomas, primarily involved amino fatty metabolism. Among these, CYB5R3 PICK1 emerged strong genetic links signals (PPH4 = 1). CYB5R3, upregulated associated enhanced elevated reactive oxygen species (ROS) production, poor outcomes (HR 2.23, P < 0.001). PICK1, despite being downregulated, showed context-dependent roles progression, expression worse prognosis 2.86, moderate predictive capacity one-year (AUC 0.695). This study highlights identifying regulators influenced GCNY. By pathways, including ROS phosphorylation activity, offers novel multitarget strategy therapy. These findings underscore importance target gliomas provide new insights into integrated management.

Language: Английский

Citations

0
The Warburg hypothesis and the emergence of the mitochondrial metabolic theory of cancer DOI Creative Commons
Thomas N. Seyfried,

Derek C. Lee,

Tomás Duraj

et al.

Journal of Bioenergetics and Biomembranes, Journal Year: 2025, Volume and Issue: unknown

Published: April 8, 2025

Abstract Otto Warburg originally proposed that cancer arose from a two-step process. The first step involved chronic insufficiency of mitochondrial oxidative phosphorylation (OxPhos), while the second protracted compensatory energy synthesis through lactic acid fermentation. His extensive findings showed oxygen consumption was lower lactate production higher in cancerous tissues than non-cancerous tissues. considered both and extracellular as accurate markers for ATP OxPhos glycolysis, respectively. Warburg’s hypothesis challenged showing remained high some cells despite elevated suggesting largely unimpaired. New information indicates neither nor are surrogates quantification cells. also did not know significant amount could come glutamine-driven substrate level glutaminolysis pathway with succinate produced end product, thus confounding linkage to origin within mitochondria. Moreover, new shows cytoplasmic lipid droplets aerobic fermentation biomarkers insufficiency. original can now be linked more complete understanding how underlies dysregulated cell growth. These address several questionable assumptions regarding allowing field advance effective therapeutic strategies less toxic metabolic management prevention cancer.

Language: Английский

Citations

0