Metabolic Fluxes in Cancer Metabolism

Günther, Ulrich L.; Chong, Mei; Volpari, Tatiana; Koczula, Katarzyna M.; Atkins, Karen; Bunce, Christopher M.; Khanim, Farhat L.

doi:10.1007/978-3-7091-1824-5_14

Cited by 6 publications

(15 citation statements)

References 140 publications

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“…Stable-isotope labelling (with an isotope such as 13 C) of a precursor (such as glucose or glutamine) enables tracking of its cellular fate in vitro or in vivo 53,73 . Datasets from such experiments can be fed into mathematical models such as metabolic flux analysis 6–9,74,75 (see Supplementary information S1 (figure)). …”

Section: State-of-the-art Technologiesmentioning

confidence: 99%

Metabolomics in rheumatic diseases: desperately seeking biomarkers

2016

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Metabolomics enables the profiling of large numbers of small molecules in cells, tissues and biological fluids. These molecules, which include amino acids, carbohydrates, lipids, nucleotides and their metabolites, can be detected quantitatively. Metabolomic methods, often focused on the information-rich analytical techniques of NMR spectroscopy and mass spectrometry, have potential for early diagnosis, monitoring therapy and defining disease pathogenesis in many therapeutic areas, including rheumatic diseases. By performing global metabolite profiling, also known as untargeted metabolomics, new discoveries linking cellular pathways to biological mechanisms are being revealed and are shaping our understanding of cell biology, physiology and medicine. These pathways can potentially be targeted to diagnose and treat patients with immune-mediated diseases.

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Section: State-of-the-art Technologiesmentioning

confidence: 99%

Metabolomics in rheumatic diseases: desperately seeking biomarkers

2016

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“…PI3K/Akt pathway promotes activation of glycolytic metabolism through Akt-mediated membrane translocation of glucose transporter (GLUT1), and AKT-dependent activation of hexokinase (HK) and phosphofructokinase-2 (PFK-2). PFK2 promotes fructose-2,6-bisphosphate’s allosteric regulation of the glycolytic enzyme phosphofructokinase-1 (PFK1) [ 37 , 42 , 43 ].…”

Section: Metabolic Pathways Associated With Cancer and Drug Resistmentioning

confidence: 99%

“…mTOR is also thought to stimulate de novo lipid synthesis. mTOR pathway plays important role in nutrient uptake, regulation of energy metabolism, and cellular survival [ 43 ]. However, mTOR is over-activated in many types of sporadic and hereditary cancers [ 44 ].…”

Section: Metabolic Pathways Associated With Cancer and Drug Resistmentioning

confidence: 99%

Cancer Metabolism and Drug Resistance

2015

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Metabolic alterations, driven by genetic and epigenetic factors, have long been known to be associated with the etiology of cancer. Furthermore, accumulating evidence suggest that cancer metabolism is intimately linked to drug resistance, which is currently one of the most important challenges in cancer treatment. Altered metabolic pathways help cancer cells to proliferate at a rate higher than normal, adapt to nutrient limited conditions, and develop drug resistance phenotypes. Application of systems biology, boosted by recent advancement of novel high-throughput technologies to obtain cancer-associated, transcriptomic, proteomic and metabolomic data, is expected to make a significant contribution to our understanding of metabolic properties related to malignancy. Indeed, despite being at a very early stage, quantitative data obtained from the omics platforms and through applications of 13C metabolic flux analysis (MFA) in in vitro studies, researchers have already began to gain insight into the complex metabolic mechanisms of cancer, paving the way for selection of molecular targets for therapeutic interventions. In this review, we discuss some of the major findings associated with the metabolic pathways in cancer cells and also discuss new evidences and achievements on specific metabolic enzyme targets and target-directed small molecules that can potentially be used as anti-cancer drugs.

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“…For SIRM applications, NMR spectroscopy has been historically used for structural elucidation of metabolic tracers by determining the site‐specific incorporation by in vivo and in vitro 13 C NMR . Alternatively, two dimensional NMR spectroscopy acquired using a large number of increments on the indirect dimension can provide 13 C‐ 13 C scalar coupling information and thus valuable information to determine the exact position of the labelled atom . 13 C NMR has been successfully applied to study tumor metabolism of primary human GBM and IDH‐mutated gliomas by infusion of 13 C‐labeled nutrients (glucose, acetate and glutamine) …”

Section: Metabolic Profile Analysis Methodsmentioning

confidence: 99%

Metabolomic signature of brain cancer

Pandey

Caflisch

Lodi

et al. 2017

Molecular Carcinogenesis

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Despite advances in surgery and adjuvant therapy, brain tumours represent one of the leading causes of cancer-related mortality and morbidity in both adults and children. Gliomas constitute about 60% of all cerebral tumours, showing varying degrees of malignancy. They are difficult to treat due to dismal prognosis and limited therapeutics. Metabolomics is the untargeted and targeted analyses of endogenous and exogenous small molecules, which characterizes the phenotype of an individual. This emerging “omics” science provides functional readouts of cellular activity that contribute greatly to the understanding of cancer biology including brain tumour biology. Metabolites are highly informative as a direct signature of biochemical activity; therefore, metabolite profiling has become a promising approach for clinical diagnostics and prognostics. The metabolic alterations are well-recognized as one of the key hallmarks in monitoring disease progression, therapy and revealing new molecular targets for effective therapeutic intervention. Taking advantage of the latest high-throughput analytical technologies, i.e. nuclear magnetic resonance spectroscopy and mass spectrometry, metabolomics is now a promising field for precision medicine and drug discovery. In the present report, we review the application of metabolomics and in vivo metabolic profiling in the context of adult gliomas and paediatric brain tumours. Analytical platforms such as high-resolution nuclear magnetic resonance, in vivo magnetic resonance spectroscopic imaging and high- and low-resolution mass spectrometry are discussed. Moreover, the relevance of metabolic studies in the development of new therapeutic strategies for treatment of gliomas are reviewed.

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Metabolic Fluxes in Cancer Metabolism

Cited by 6 publications

References 140 publications

Metabolomics in rheumatic diseases: desperately seeking biomarkers

Metabolomics in rheumatic diseases: desperately seeking biomarkers

Cancer Metabolism and Drug Resistance

Metabolomic signature of brain cancer

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