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      Monitoring cancer prognosis, diagnosis and treatment efficacy using metabolomics and lipidomics

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          Abstract

          Introduction

          Cellular metabolism is altered during cancer initiation and progression, which allows cancer cells to increase anabolic synthesis, avoid apoptosis and adapt to low nutrient and oxygen availability. The metabolic nature of cancer enables patient cancer status to be monitored by metabolomics and lipidomics. Additionally, monitoring metabolic status of patients or biological models can be used to greater understand the action of anticancer therapeutics.

          Objectives

          Discuss how metabolomics and lipidomics can be used to (i) identify metabolic biomarkers of cancer and (ii) understand the mechanism-of-action of anticancer therapies. Discuss considerations that can maximize the clinical value of metabolic cancer biomarkers including case–control, prognostic and longitudinal study designs.

          Methods

          A literature search of the current relevant primary research was performed.

          Results

          Metabolomics and lipidomics can identify metabolic signatures that associate with cancer diagnosis, prognosis and disease progression. Discriminatory metabolites were most commonly linked to lipid or energy metabolism. Case–control studies outnumbered prognostic and longitudinal approaches. Prognostic studies were able to correlate metabolic features with future cancer risk, whereas longitudinal studies were most effective for studying cancer progression. Metabolomics and lipidomics can help to understand the mechanism-of-action of anticancer therapeutics and mechanisms of drug resistance.

          Conclusion

          Metabolomics and lipidomics can be used to identify biomarkers associated with cancer and to better understand anticancer therapies.

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          Most cited references72

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          On the origin of cancer cells.

          O WARBURG (1956)
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            Targeting lactate metabolism for cancer therapeutics.

            Lactate, once considered a waste product of glycolysis, has emerged as a critical regulator of cancer development, maintenance, and metastasis. Indeed, tumor lactate levels correlate with increased metastasis, tumor recurrence, and poor outcome. Lactate mediates cancer cell intrinsic effects on metabolism and has additional non-tumor cell autonomous effects that drive tumorigenesis. Tumor cells can metabolize lactate as an energy source and shuttle lactate to neighboring cancer cells, adjacent stroma, and vascular endothelial cells, which induces metabolic reprogramming. Lactate also plays roles in promoting tumor inflammation and in functioning as a signaling molecule that stimulates tumor angiogenesis. Here we review the mechanisms of lactate production and transport and highlight emerging evidence indicating that targeting lactate metabolism is a promising approach for cancer therapeutics.
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              MYC/PGC-1α Balance Determines the Metabolic Phenotype and Plasticity of Pancreatic Cancer Stem Cells.

              The anti-diabetic drug metformin targets pancreatic cancer stem cells (CSCs), but not their differentiated progenies (non-CSCs), which may be related to distinct metabolic phenotypes. Here we conclusively demonstrate that while non-CSCs were highly glycolytic, CSCs were dependent on oxidative metabolism (OXPHOS) with very limited metabolic plasticity. Thus, mitochondrial inhibition, e.g., by metformin, translated into energy crisis and apoptosis. However, resistant CSC clones eventually emerged during treatment with metformin due to their intermediate glycolytic/respiratory phenotype. Mechanistically, suppression of MYC and subsequent increase of PGC-1α were identified as key determinants for the OXPHOS dependency of CSCs, which was abolished in resistant CSC clones. Intriguingly, no resistance was observed for the mitochondrial ROS inducer menadione and resistance could also be prevented/reversed for metformin by genetic/pharmacological inhibition of MYC. Thus, the specific metabolic features of pancreatic CSCs are amendable to therapeutic intervention and could provide the basis for developing more effective therapies to combat this lethal cancer.
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                Author and article information

                Contributors
                a.d.southam@bham.ac.uk
                Journal
                Metabolomics
                Metabolomics
                Metabolomics
                Springer US (New York )
                1573-3882
                1573-3890
                16 August 2016
                16 August 2016
                2016
                : 12
                : 146
                Affiliations
                [1 ]Centre for Metabolomics and Bioanalysis (CEMBIO), Faculty of Pharmacy, Universidad CEU San Pablo, Campus Monteprincipe, Boadilla del Monte, 28668 Madrid, Spain
                [2 ]Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8TA UK
                [3 ]Glasgow Polyomics, Wolfson Wohl Cancer Research Centre, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, G61 1QH UK
                [4 ]School of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT UK
                Author information
                http://orcid.org/0000-0003-3030-7663
                Article
                1093
                10.1007/s11306-016-1093-7
                4987388
                27616976
                d29a0282-6073-4511-8829-bb6b58e7eede
                © The Author(s) 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 17 May 2016
                : 2 August 2016
                Funding
                Funded by: Bloodwise
                Funded by: Spanish Ministry of Science and Technology
                Award ID: CTQ2014-55279-R
                Award Recipient :
                Categories
                Original Article
                Custom metadata
                © Springer Science+Business Media New York 2016

                Molecular biology
                mass spectrometry,nuclear magnetic resonance,leukemia,stratified medicine,nutraceutical,drug redeployment

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