ArticleMolecular cancer therapeutics2016
MR Studies of Glioblastoma Models Treated with Dual PI3K/mTOR Inhibitor and Temozolomide:Metabolic Changes Are Associated with Enhanced Survival.
Article in Molecular cancer therapeutics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 44 citations in OpenAlex.
- Evaluation of treatment response in patients with recurrent grade 4 glioma using hyperpolarized [1-Research square · 2026Article
- Voxtalisib inhibits enterovirus 71 replication by downregulating host RAN and restoring IFN-STAT signaling.Journal of advanced research · 2026Article
- Predictive efficacy and role of 2HG in MGMT promoter methylation in gliomas: a retrospective study based on MRS and mediator variable analysis.British journal of cancer · 2025Article
- Integrative genomic analysis facilitates precision strategies for glioblastoma treatment.iScience · 2022Article
- Imaging Glioblastoma Metabolism by Using Hyperpolarized [1-Radiology. Imaging cancer · 2022Article
- Acquisition and quantification pipeline for in vivo hyperpolarizedMagnetic resonance in medicine · 2022Article
- Specialized computational methods for denoising, BMagnetic resonance in medicine · 2021Article
- Detection of metabolic change in glioblastoma cells after radiotherapy using hyperpolarizedNMR in biomedicine · 2021Article
- The PI3K Inhibitor XH30 Enhances Response to Temozolomide in Drug-Resistant GlioblastomaFrontiers in pharmacology · 2021Article
- Tumor treating fields (TTFields) impairs aberrant glycolysis in glioblastoma as evaluated by [Neoplasia (New York, N.Y.) · 2021Article
- Glutamate Is a Noninvasive Metabolic Biomarker of IDH1-Mutant Glioma Response to Temozolomide Treatment.Cancer research · 2020Article
- Intratumoral Distribution of Lactate and the Monocarboxylate Transporters 1 and 4 in Human Glioblastoma Multiforme and Their Relationships to Tumor Progression-Associated Markers.International journal of molecular sciences · 2020Article
- In vivo detection of γ-glutamyl-transferase up-regulation in glioma using hyperpolarized γ-glutamyl-[1-Scientific reports · 2020Article
- Evaluation of Glycolytic Response to Multiple Classes of Anti-glioblastoma Drugs by Noninvasive Measurement of Pyruvate Kinase M2 Using [Molecular imaging and biology · 2020Article
- Hyperpolarized Pyruvate MR Spectroscopy Depicts Glycolytic Inhibition in a Mouse Model of Glioma.Radiology · 2019Article
- Next Generation Sequencing-Based Transcriptome Predicts Bevacizumab Efficacy in Combination with Temozolomide in Glioblastoma.Molecules (Basel, Switzerland) · 2019Article
- PI3K/mTOR inhibition of IDH1 mutant glioma leads to reduced 2HG production that is associated with increased survival.Scientific reports · 2019Article
- HDAC inhibition in glioblastoma monitored by hyperpolarizedNMR in biomedicine · 2019Article
- Hyperpolarized MRI Visualizes Warburg Effects and Predicts Treatment Response to mTOR Inhibitors in Patient-Derived ccRCC Xenograft Models.Cancer research · 2019Article
- Dual PI3K/mTOR Inhibitor, XL765, suppresses glioblastoma growth by inducing ER stress-dependent apoptosis.OncoTargets and therapy · 2019Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The current standard of care for glioblastoma (GBM) is surgical resection, radiotherapy, and treatment with temozolomide (TMZ). However, resistance to current therapies and recurrence are common. To improve survival, agents that target the PI3K signaling pathway, which is activated in approximately 88% of GBM, are currently in clinical trials. A challenge with such therapies is that tumor shrinkage is not always observed. New imaging methods are therefore needed to monitor response to therapy and predict survival. The goal of this study was to determine whether hyperpolarized (13)C magnetic resonance spectroscopic imaging (MRSI) and (1)H magnetic resonance spectroscopy (MRS) can be used to monitor response to the second-generation dual PI3K/mTOR inhibitor voxtalisib (XL765, SAR245409), alone or in combination with TMZ. We investigated GS-2 and U87-MG GBM orthotopic tumors in mice, and used MRI, hyperpolarized (13)C MRSI, and (1)H MRS to monitor the effects of treatment. In our study, (1)H MRS could not predict tumor response to therapy. However, in both our models, we observed a significantly lower hyperpolarized lactate-to-pyruvate ratio in animals treated with voxtalisib, TMZ, or combination therapy, when compared with controls. This metabolic alteration was observed prior to MRI-detectable changes in tumor size, was consistent with drug action, and was associated with enhanced animal survival. Our findings confirm the potential translational value of the hyperpolarized lactate-to-pyruvate ratio as a biomarker for noninvasively assessing the effects of emerging therapies for patients with GBM. Mol Cancer Ther; 15(5); 1113-22. ©2016 AACR.
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