Multinuclear NMR and MRI reveal an early metabolic response to mTOR inhibition in sarcoma Journal Article


Authors: Di Gialleonardo, V.; Aldeborgh, H. N.; Miloushev, V.; Folkers, K. M.; Granlund, K.; Tap, W. D.; Lewis, J. S.; Weber, W. A.; Keshari, K. R.
Article Title: Multinuclear NMR and MRI reveal an early metabolic response to mTOR inhibition in sarcoma
Abstract: Biomarkers predicting rapalog responses in sarcomas where PI3K and mTOR are often hyperactivated could improve the suitable recruitment of responsive patients to clinical trials. PI3K/mTOR pathway activation drives energy production by regulating anaerobic glycolysis in cancer cells, suggesting a route toward a monitoring strategy. In this study, we took a multimodality approach to evaluate the phenotypic effects and metabolic changes that occur with inhibition of the PI3K/mTOR pathway. Its central role in regulating glycolysis in human sarcomas was evaluated by short- and long-term rapamycin treatment in sarcoma cell lines. We observed an overall decrease in lactate production in vitro, followed by cell growth inhibition. In vivo, we observed a similar quantitative reduction in lactate production as monitored by hyperpolarized MRI, also followed by tumor size changes. This noninvasive imaging method could distinguish reduced cell proliferation from induction of cell death. Our results illustrate the use of hyperpolarized MRI as a sensitive technique to monitor drug-induced perturbation of the PI3K/mTOR pathway in sarcomas. ©2017 AACR.
Journal Title: Cancer Research
Volume: 77
Issue: 11
ISSN: 0008-5472
Publisher: American Association for Cancer Research  
Date Published: 2017-06-01
Start Page: 3113
End Page: 3120
Language: English
DOI: 10.1158/0008-5472.can-16-3310
PROVIDER: scopus
PMCID: PMC5457322
PUBMED: 28386017
DOI/URL:
Notes: Article -- Export Date: 3 July 2017 -- Source: Scopus
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  1. Jason S Lewis
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  2. William Douglas Tap
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  3. Wolfgang Andreas Weber
    172 Weber