NMR-based stable isotope resolved metabolomics was used to characterize small cell neuroendocrine (SCNC) and adenocarcinoma (aCRPC) subtypes of castration-resistant prostate cancer patient-derived xenografts (PDXs). Targeted metabolomics indicated distinct upregulation of metabolic pathways in SCNC relative to aCRPC PDXs. Specifically, [U-13C]glucose and [U-13C]glutamine labeling demonstrated that SCNC PDXs had increased glycolytic rate, alanine aminotransferase and tricarboxylic acid cycle activity, including anaplerotic sources. Further, the metabolic differences observed among the aCRPC and SCNC PDXs exhibited a continuous range as predicted by clinical genomic data of these subtypes of CRPC.
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