Article

Magnetic Resonance Spectroscopy Detectable Metabolomic Fingerprint of Response to Antineoplastic Treatment

Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, United States of America.
PLoS ONE (Impact Factor: 3.23). 10/2011; 6(10):e26155. DOI: 10.1371/journal.pone.0026155
Source: PubMed

ABSTRACT

Targeted therapeutic approaches are increasingly being implemented in the clinic, but early detection of response frequently presents a challenge as many new therapies lead to inhibition of tumor growth rather than tumor shrinkage. Development of novel non-invasive methods to monitor response to treatment is therefore needed. Magnetic resonance spectroscopy (MRS) and magnetic resonance spectroscopic imaging are non-invasive imaging methods that can be employed to monitor metabolism, and previous studies indicate that these methods can be useful for monitoring the metabolic consequences of treatment that are associated with early drug target modulation. However, single-metabolite biomarkers are often not specific to a particular therapy. Here we used an unbiased 1H MRS-based metabolomics approach to investigate the overall metabolic consequences of treatment with the phosphoinositide 3-kinase inhibitor LY294002 and the heat shock protein 90 inhibitor 17AAG in prostate and breast cancer cell lines. LY294002 treatment resulted in decreased intracellular lactate, alanine fumarate, phosphocholine and glutathione. Following 17AAG treatment, decreased intracellular lactate, alanine, fumarate and glutamine were also observed but phosphocholine accumulated in every case. Furthermore, citrate, which is typically observed in normal prostate tissue but not in tumors, increased following 17AAG treatment in prostate cells. This approach is likely to provide further information about the complex interactions between signaling and metabolic pathways. It also highlights the potential of MRS-based metabolomics to identify metabolic signatures that can specifically inform on molecular drug action.

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Available from: Sabrina M Ronen
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    • "During the TORAVA trial, several translational studies have been set up to highlight predictive markers of the response and clinical outcome (i.e., toxicity). An increasing number of metabolomic studies in oncology, carried out on diverse types of biological samples (tumour cells, blood serum and so on) aim at highlighting biomarkers to distinguish various cancerous states (Oakman et al, 2011; Jobard et al, 2014), biomarkers of treatment response and toxicity to probe the molecular action of drugs, as well as resistance phenomena (Lodi and Ronen, 2011; Tenori et al, 2012; Weaver et al, 2012; Borgan et al, 2013; Wei et al, 2013). "
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