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Ganti S, et al., Kidney Tumor Biomarkers Revealed by Simultaneous Multiple Matrix Metabolomics Analysis. Cancer Res, 2012.

SYNOPSIS

Metabolon results led to:
Identification of metabolite signatures that translate from the human to the mouse
Identification of a potential new targets for kidney cancer

Key metabolomic observations:
Altered metabolites in the tryptophan degradation pathway
Metabolic changes that point to PPAR-alpha dysregulation in kidney cancer

Synopsis
Biomarkers and new targets for kidney cancer are needed to improve diagnosis and treatment. In previous work, investigators discovered several distinguishing pathways in the urine of subjects with kidney cancer. To extend these findings, samples from a mouse xenograft were profiled by metabolomics. Metabolites of the tryptophan degradation pathway exhibited a particularly strong concordance between the mouse and human. PPAR-alpha is known to regulate enzymes in this pathway and additional metabolites corroborated the potential for PPAR-alpha to have a mechanistic link to kidney cancer. Indeed, it was shown that modulation of PPAR-alpha altered proliferation of cancer cell lines and inhibition of enzymes in the tryptophan pathway resulted in the suppression of the inflammatory response (suggesting that kidney tumors may evade immune surveillance by increasing tryptophan metabolism). In summary, this work illustrates the translatability of metabolites across disease models with the potential to turn these signatures into therapeutic targets.

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