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      A Review of Applications of Metabolomics in Cancer

      review-article
      Metabolites
      MDPI
      cancer, metabolomics, metabonomics, personalized medicine, biomarker

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          Abstract

          Cancer is a devastating disease that alters the metabolism of a cell and the surrounding milieu. Metabolomics is a growing and powerful technology capable of detecting hundreds to thousands of metabolites in tissues and biofluids. The recent advances in metabolomics technologies have enabled a deeper investigation into the metabolism of cancer and a better understanding of how cancer cells use glycolysis, known as the “Warburg effect,” advantageously to produce the amino acids, nucleotides and lipids necessary for tumor proliferation and vascularization. Currently, metabolomics research is being used to discover diagnostic cancer biomarkers in the clinic, to better understand its complex heterogeneous nature, to discover pathways involved in cancer that could be used for new targets and to monitor metabolic biomarkers during therapeutic intervention. These metabolomics approaches may also provide clues to personalized cancer treatments by providing useful information to the clinician about the cancer patient’s response to medical interventions.

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          Most cited references141

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          On the origin of cancer cells.

          O WARBURG (1956)
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            Metabolomics--the link between genotypes and phenotypes.

            Metabolites are the end products of cellular regulatory processes, and their levels can be regarded as the ultimate response of biological systems to genetic or environmental changes. In parallel to the terms 'transcriptome' and proteome', the set of metabolites synthesized by a biological system constitute its 'metabolome'. Yet, unlike other functional genomics approaches, the unbiased simultaneous identification and quantification of plant metabolomes has been largely neglected. Until recently, most analyses were restricted to profiling selected classes of compounds, or to fingerprinting metabolic changes without sufficient analytical resolution to determine metabolite levels and identities individually. As a prerequisite for metabolomic analysis, careful consideration of the methods employed for tissue extraction, sample preparation, data acquisition, and data mining must be taken. In this review, the differences among metabolite target analysis, metabolite profiling, and metabolic fingerprinting are clarified, and terms are defined. Current approaches are examined, and potential applications are summarized with a special emphasis on data mining and mathematical modelling of metabolism.
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              Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression.

              Multiple, complex molecular events characterize cancer development and progression. Deciphering the molecular networks that distinguish organ-confined disease from metastatic disease may lead to the identification of critical biomarkers for cancer invasion and disease aggressiveness. Although gene and protein expression have been extensively profiled in human tumours, little is known about the global metabolomic alterations that characterize neoplastic progression. Using a combination of high-throughput liquid-and-gas-chromatography-based mass spectrometry, we profiled more than 1,126 metabolites across 262 clinical samples related to prostate cancer (42 tissues and 110 each of urine and plasma). These unbiased metabolomic profiles were able to distinguish benign prostate, clinically localized prostate cancer and metastatic disease. Sarcosine, an N-methyl derivative of the amino acid glycine, was identified as a differential metabolite that was highly increased during prostate cancer progression to metastasis and can be detected non-invasively in urine. Sarcosine levels were also increased in invasive prostate cancer cell lines relative to benign prostate epithelial cells. Knockdown of glycine-N-methyl transferase, the enzyme that generates sarcosine from glycine, attenuated prostate cancer invasion. Addition of exogenous sarcosine or knockdown of the enzyme that leads to sarcosine degradation, sarcosine dehydrogenase, induced an invasive phenotype in benign prostate epithelial cells. Androgen receptor and the ERG gene fusion product coordinately regulate components of the sarcosine pathway. Here, by profiling the metabolomic alterations of prostate cancer progression, we reveal sarcosine as a potentially important metabolic intermediary of cancer cell invasion and aggressivity.
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                Author and article information

                Journal
                Metabolites
                Metabolites
                metabolites
                Metabolites
                MDPI
                2218-1989
                05 July 2013
                September 2013
                : 3
                : 3
                : 552-574
                Affiliations
                National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA; E-Mail: Richard.Beger@ 123456fda.hhs.gov ; Tel.: +870-543-7080; Fax: +870-543-7686.
                Article
                metabolites-03-00552
                10.3390/metabo3030552
                3901293
                24958139
                eb9db740-e35e-43ae-babf-79cad45585a3
                © 2013 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 24 April 2013
                : 17 May 2013
                : 24 June 2013
                Categories
                Review

                cancer,metabolomics,metabonomics,personalized medicine,biomarker

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