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Metabolite profiling stratifies pancreatic ductal adenocarcinomas into subtypes with distinct sensitivities to metabolic inhibitors

Daemen, A., Peterson, D., Sahu, N., et al.

Targeting cancer metabolism requires personalized diagnostics for clinical success. Pancreatic ductal adenocarcinoma (PDAC) is characterized by metabolism addiction. To identify metabolic dependencies within PDAC, we conducted broad metabolite profiling and identified three subtypes that showed distinct metabolite profiles associated with glycolysis, lipogenesis, and redox pathways. Importantly, these profiles significantly correlated with enriched sensitivity to a variety of metabolic inhibitors including inhibitors targeting glycolysis, glutaminolysis, lipogenesis, and redox balance. In primary PDAC tumor samples, the lipid subtype was strongly associated with an epithelial phenotype, whereas the glycolytic subtype was strongly associated with a mesenchymal phenotype, suggesting functional relevance in disease progression. Our findings will provide valuable predictive utility for a number of metabolic inhibitors currently undergoing phase I testing.

Citation

Daemen, A., Peterson, D., Sahu, N., et al. "Metabolite profiling stratifies pancreatic ductal adenocarcinomas into subtypes with distinct sensitivities to metabolic inhibitors" Proceedings of the National Academy of Sciences of the United States of America (2015): E4,410–7