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Metabolic Pathway Analysis in Cancer
Author(s) -
DeBerardinis Ralph J
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.327.3
Subject(s) - cancer cell , metabolomics , glutamine , cancer , metabolism , metabolic pathway , cell metabolism , biology , warburg effect , cell , cell culture , computational biology , biochemistry , extracellular , reprogramming , metabolic flux analysis , tumor microenvironment , cancer research , tumor cells , bioinformatics , amino acid , genetics
Reprogramming of cellular metabolism is a hallmark of malignancy. Understanding the metabolic transitions that accompany cellular transformation will lead to new insights into the biological basis of transformation, and may generate new targets for therapy and diagnostic imaging in cancer. We use a combination of NMR spectroscopy and mass spectrometry to analyze tumor cell metabolism in culture, in mouse models of cancer, and in human patients. Analysis of nearly 100 individual cell culture models uncovered a surprising amount of cell‐autonomous metabolic heterogeneity, but also demonstrated that most cancer cells can be stratified into a finite subset of metabolic platforms according to how they metabolize glucose and glutamine, two abundant extracellular nutrients that account for the bulk of carbon and nitrogen metabolism in cancer cells. We have now developed isotope tracing methods to probe intermediary metabolism in live tumors, both in mice and in humans. This work revealed the appearance of many of the same metabolic activities in vivo as those observed in cultured cells, including glucose oxidation, anaplerosis, and amino acid synthesis. Our ongoing work seeks to develop methods to translate these findings into novel imaging approaches to diagnose cancer and monitor the response to therapy.