ArticleActa neuropathologica2015
Bevacizumab treatment induces metabolic adaptation toward anaerobic metabolism in glioblastomas.
Article in Acta neuropathologica, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 1 of them a synthesis that pooled it.
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Who cites it
92 citing papers in PubMed, 1 synthesis or guideline pooled it, 145 citations in OpenAlex.
- A Systematic Review of the Metabolism of High-Grade Gliomas: Current Targeted Therapies and Future Perspectives.International journal of molecular sciences · 2024Pooled it
- Metabolic consequences of perioperative oral carbohydrates in breast cancer patients - an explorative study.BMC cancer · 2019Trial
- Biological basis and clinical study of glycogen synthase kinase- 3β-targeted therapy by drug repositioning for glioblastoma.Oncotarget · 2017Trial
- Randomized phase II study of axitinib versus physicians best alternative choice of therapy in patients with recurrent glioblastoma.Journal of neuro-oncology · 2016Trial
- Evaluation of treatment response in patients with recurrent grade 4 glioma using hyperpolarized [1-Research square · 2026Article
- Article
- Case report of three patients with end-stage recurrent glioblastoma treated with meldonium.BJC reports · 2025Article
- Endothelial-secreted Endocan activates PDGFRA and regulates vascularity and spatial phenotype in glioblastoma.Nature communications · 2025Article
- Matrix Protein of Vesicular Stomatitis Virus Targets the Mitochondria, Reprograms Glucose Metabolism, and Sensitizes to 2-Deoxyglucose in Glioblastoma.Human gene therapy · 2024Article
- Comprehensive analysis to identify the relationship between CALD1 and immune infiltration in glioma.Translational cancer research · 2024Article
- Glioblastoma-instructed microglia transition to heterogeneous phenotypic states with phagocytic and dendritic cell-like features in patient tumors and patient-derived orthotopic xenografts.Genome medicine · 2024Article
- Article
- SUMOylation modification of HNRNPK at the K422 site promotes invasion in glioblastoma.International journal of biological sciences · 2024Article
- Glioblastoma-instructed microglia transition to heterogeneous phenotypic states with phagocytic and dendritic cell-like features in patient tumors and patient-derived orthotopic xenografts.bioRxiv : the preprint server for biology · 2023Article
- Anaplerotic nutrient stress drives synergy of angiogenesis inhibitors with therapeutics targeting tumor metabolism.bioRxiv : the preprint server for biology · 2023Article
- Glioblastoma Metabolism: Insights and Therapeutic Strategies.International journal of molecular sciences · 2023Review
- Mechanisms of Acquired Resistance to Anti-VEGF Therapy for Neovascular Eye Diseases.Investigative ophthalmology & visual science · 2023Review
- Non-metabolic functions of phosphofructokinase-1 orchestrate tumor cellular invasion and genome maintenance under bevacizumab therapy.Neuro-oncology · 2023Article
- Vascular co-option in resistance to anti-angiogenic therapy.Frontiers in oncology · 2023Review
- PotentFrontiers in oncology · 2023Article
32 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 7 institutions in 4 countries.
Funding
Abstract
Anti-angiogenic therapy in glioblastoma (GBM) has unfortunately not led to the anticipated improvement in patient prognosis. We here describe how human GBM adapts to bevacizumab treatment at the metabolic level. By performing (13)C6-glucose metabolic flux analysis, we show for the first time that the tumors undergo metabolic re-programming toward anaerobic metabolism, thereby uncoupling glycolysis from oxidative phosphorylation. Following treatment, an increased influx of (13)C6-glucose was observed into the tumors, concomitant to increased lactate levels and a reduction of metabolites associated with the tricarboxylic acid cycle. This was confirmed by increased expression of glycolytic enzymes including pyruvate dehydrogenase kinase in the treated tumors. Interestingly, L-glutamine levels were also reduced. These results were further confirmed by the assessment of in vivo metabolic data obtained by magnetic resonance spectroscopy and positron emission tomography. Moreover, bevacizumab led to a depletion in glutathione levels indicating that the treatment caused oxidative stress in the tumors. Confirming the metabolic flux results, immunohistochemical analysis showed an up-regulation of lactate dehydrogenase in the bevacizumab-treated tumor core as well as in single tumor cells infiltrating the brain, which may explain the increased invasion observed after bevacizumab treatment. These observations were further validated in a panel of eight human GBM patients in which paired biopsy samples were obtained before and after bevacizumab treatment. Importantly, we show that the GBM adaptation to bevacizumab therapy is not mediated by clonal selection mechanisms, but represents an adaptive response to therapy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.