ArticleNeuro-oncology2012
Reduced phosphocholine and hyperpolarized lactate provide magnetic resonance biomarkers of PI3K/Akt/mTOR inhibition in glioblastoma.
Article in Neuro-oncology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
66 citing papers in PubMed, 94 citations in OpenAlex.
- Trial
- Evaluation of treatment response in patients with recurrent grade 4 glioma using hyperpolarized [1-Research square · 2026Article
- Lactylation in cancer biology: Unlocking new avenues for research and therapy.Cancer communications (London, England) · 2025Review
- GLUT1 as a Potential Therapeutic Target in Glioblastoma.Brain sciences · 2025Review
- Current advance of nanotechnology in diagnosis and treatment for malignant tumors.Signal transduction and targeted therapy · 2024Review
- CRISPR-Cas9 identifies growth-related subtypes of glioblastoma with therapeutical significance through cell line knockdown.BMC cancer · 2023Article
- Hyperpolarized δ-[1-Scientific reports · 2023Article
- At a crossroads: how to translate the roles of PI3K in oncogenic and metabolic signalling into improvements in cancer therapy.Nature reviews. Clinical oncology · 2022Review
- Dandelion extract inhibits triple-negative breast cancer cell proliferation by interfering with glycerophospholipids and unsaturated fatty acids metabolism.Frontiers in pharmacology · 2022Article
- In Vivo Assessment of Metabolic Abnormality in Alport Syndrome Using Hyperpolarized [1-Metabolites · 2021Article
- HyperpolarizedScientific reports · 2021Article
- Metabolic Imaging Detects Resistance to PI3Kα Inhibition Mediated by Persistent FOXM1 Expression in ERCancer cell · 2020Article
- Autophagy as a Potential Therapy for Malignant Glioma.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Metabolic Control of Epilepsy: A Promising Therapeutic Target for Epilepsy.Frontiers in neurology · 2020Review
- Insights into the Chemical Biology of Childhood Embryonal Solid Tumors by NMR-Based Metabolomics.Biomolecules · 2019Review
- PI3K/mTOR inhibition of IDH1 mutant glioma leads to reduced 2HG production that is associated with increased survival.Scientific reports · 2019Article
- Ex vivo metabolite profiling of paediatric central nervous system tumours reveals prognostic markers.Scientific reports · 2019Article
- Magnetic Resonance Imaging Is More Sensitive Than PET for Detecting Treatment-Induced Cell Death-Dependent Changes in Glycolysis.Cancer research · 2019Article
- Combination treatment of cancer cells with pan-Akt and pan-mTOR inhibitors: effects on cell cycle distribution, p-Akt expression level and radiolabelled-choline incorporation.Investigational new drugs · 2019Article
- HyperpolarizedRadiology · 2019Review
6 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
6 authors at 2 institutions in 1 country.
Funding
Abstract
The phosphatidylinositol-3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway is activated in more than88% of glioblastomas (GBM). New drugs targeting this pathway are currently in clinical trials. However, noninvasive assessment of treatment response remains challenging. By using magnetic resonance spectroscopy (MRS), PI3K/Akt/mTOR pathway inhibition was monitored in 3 GBM cell lines (GS-2, GBM8, and GBM6; each with a distinct pathway activating mutation) through the measurement of 2 mechanistically linked MR biomarkers: phosphocholine (PC) and hyperpolarized lactate.(31)P MRS studies showed that treatment with the PI3K inhibitor LY294002 induced significant decreases in PC to 34 %± 9% of control in GS-2 cells, 48% ± 5% in GBM8, and 45% ± 4% in GBM6. The mTOR inhibitor everolimus also induced a significant decrease in PC to 62% ± 14%, 57% ± 1%, and 58% ± 1% in GS-2, GBM8, and GBM6 cells, respectively. Using hyperpolarized (13)C MRS, we demonstrated that hyperpolarized lactate levels were significantly decreased following PI3K/Akt/mTOR pathway inhibition in all 3 cell lines to 51% ± 10%, 62% ± 3%, and 58% ± 2% of control with LY294002 and 72% ± 3%, 61% ± 2%, and 66% ± 3% of control with everolimus in GS-2, GBM8, and GBM6 cells, respectively. These effects were mediated by decreases in the activity and expression of choline kinase α and lactate dehydrogenase, which respectively control PC and lactate production downstream of HIF-1. Treatment with the DNA damaging agent temozolomide did not have an effect on either biomarker in any cell line. This study highlights the potential of PC and hyperpolarized lactate as noninvasive MR biomarkers of response to targeted inhibitors in GBM.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.