NMR-based metabolomics: translational application and treatment of cancer

Abstract

Cancer cells possess a highly unique metabolic phenotype which is characterized by high glucose uptake, increased glycolytic activity, decreased mitochondrial activity, low bioenergetic expenditure and increased phospholipid turnover. In addition to these general metabolic markers of malignancy, tissue-specific biochemistry has identified specific endogenous metabolites found in particular tumors types. These include N-acetyl aspartate in neuroblastoma, myo-inositol in gliomas and citrate in prostate cancer. Metabolic profiles can be readily assessed to monitor responsiveness and the development of resistance to novel targeted drugs, for example, where a cytostatic effect rather than cytotoxicity occurs. Using modern analytical technologies in combination with statistical approaches, a methodology termed 'metabolomics' has been developed. Metabolomics has been used to generate a global metabolic profile on patient samples, which can then be used to determine treatment response. This review describes existing NMR-based approaches for global metabolic profiling in tissue biopsies and body fluids and the use of non-invasive radiological techniques to assess metabolic biomarkers. In addition, studies on metabolic responses to novel targeted drugs, including tyrosine kinase inhibitors and metabolic modulators, are evaluated.