Chinnaiyan P, et al., The Metabolomic Signature of Malignant Glioma Reflects Accelerated Anabolic Metabolism. Cancer Research, 2012. 72(22): 5878-5888.
Metabolon results led to:
- Identification of metabolite signatures of glioma progression
- Identification of a metabolic enzyme as a potential drug target
Key metabolomic observations:
- Altered pyruvate kinase regulation allows glucose to feed anabolic pathways in malignant gliomas
- Metabolomic signatures predicted median patient survival more robustly than tumor grade
Glioma tumors have long been known to have grade-associated increases in glucose uptake, but the role of metabolic changes in driving cancer progression had not been studied. Global metabolic profiling of Grade II, III and IV glioma tissue from human patients identified glycolysis intermediates 3-phosphoglycerate and phosphoenolpyruvate (PEP) among the top biochemicals that contributed to tumor grade classification. This metabolite signature led to the discovery that changes in pyruvate kinase gene expression may facilitate glioma malignancy by causing glycolysis intermediates to be shunted into anabolic pathways that support rapidly dividing cells. Unbiased hierarchical clustering of metabolite profiles identified “metabolomic subtypes” within Grade III and Grade IV that had prognostic relevance in predicting median patient survival. Together these results illustrate the utility of metabolomics for identifying aggressive cancers and identifying new targets for cancer therapy.