Systems-Level Analysis of Cancer Metabolism

  • Paulo A. Gameiro
  • Christian M. Metallo
  • Gregory Stephanopoulos


The complexity of cancer requires systems-level approaches to examine uncontrolled proliferation, with many analytical tools now providing massive information on distinct cellular processes. In contrast to the genetic anchors founded in cancer biology that underpin tumor suppressors and oncogenes as units of malignant function, we now see a shift of attention towards metabolism. This trend calls for the increased use of stable isotopic tracers to dissect effects in metabolic fluxes that arise from gene deregulation. When combined with analytical techniques such as mass spectrometry or nuclear magnetic resonance (NMR) and computational tools to interpret such datasets, isotopic tracers can allow for the determination of various metabolic events involved in tumorigenesis at a fine resolution. As such, the interplay between fluxes and signaling warrants a thorough investigation that will lead to targeted therapies rooted on metabolic targets. This chapter describes stable isotopic methods to determine fluxes and identify switches, illustrating how metabolic activity can be quantitatively interpreted to address fundamental questions in cancer.


Systems-level analysis Cancer metabolism Cell proliferation Tumor repressor Oncogenes Malignent function Isotopic tracers Nuclear magnetic resonance (NMR) Metabolic flux analysis Anabolic switch Metabolic targets Lipid synthesis Nucleic acid synthesis Protein synthesis Cell culture Tumorgenesis Metabolic markers Metabolomics Mass spectrometry Isotopic enrichment Experimental design Turnover rates Metabolic steady-state Pulse-chase strategy Isotopomer distribution Elemental tracers Non-targeted tracer fate detection (NTFD) Warburg effect Metabolic switch Splice isoform Pyruvate kinase Glutamine Metabolic reprogramming Catabolic arrest 







ATP citrate lyase


Adenosine 5′-monophosphate


AMP-activated protein kinase


Adenosine 5′-triphosphate




De novo nucleoside synthesis


deoxyribose (dR)


Electron impact


Elementary metabolic unit


Electron transport chain


Fumarate hydratase


Fractional synthesis rate


Glyceraldehyde 3-phosphate


Gas Chromatography


Hexokinase II


Isocitrate dehydrogenase


Isopotomer spectral analysis


Liquid Chromatography


Lactate dehydrogenase A


Metabolic flux analysis


Mass isotopomer distribution


Mass-to-charge ratio


Non-essential amino acid


Nonstationary metabolic flux analysis


Non-targeted tracer fate detection


Oxidative phosphorylation


Pyruvate carboxylase


Pyruvate dehydrogenase




Phosphoglycerate mutase


Pyruvate kinase


Pentose phosphate pathway




Tricarboxylic acid


Transforming growth factor β






Voltage-dependent anionic channel


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Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Paulo A. Gameiro
    • 1
    • 2
    • 3
  • Christian M. Metallo
    • 1
  • Gregory Stephanopoulos
    • 1
  1. 1.Department of Chemical EngineeringMassachusetts Institute of TechnologyCambridgeUSA
  2. 2.Department of Life SciencesUniversity of CoimbraCoimbraPortugal
  3. 3.Department of MedicineMassachusetts General HospitalBostonUSA

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