Metabolite profiling stratifies pancreatic ductal adenocarcinomas into subtypes with distinct sensitivities to metabolic inhibitors
Open accessAbstract
Significance: 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.
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Differential metabolism of tumor regions can be observed through imaging techniques, including spatial heterogeneity of glycolysis.
“The differential metabolism of these regions can be readily observed through imaging techniques236,237, including spatial heterogeneity of glycolysis.”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [237]
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- Authors
- Daemen, A., Peterson, D., Sahu, N., McCord, R., Du, X., Liu, B., Kowanetz, K., Hong, R., Moffat, J., Gao, M., Boudreau, A., Mroue, R., Corson, L., O’Brien, T., Qing, J., Sampath, D., Merchant, M., Yauch, R., Manning, G., Settleman, J., Hatzivassiliou, G., & Evangelista, M.
- Affiliations
- Genentech (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2015-07-27
- Volume
- 112
- Issue
- 32
- Pages
- E4410-7
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4538616
- OpenAlex
- W1940824108
- Cited by
- 398
- References
- 60
- Citations by year
- 2026: 24 · 2025: 31 · 2024: 47 · 2023: 34 · 2022: 58 · 2021: 45 · 2020: 43 · 2019: 34 · 2018: 27 · 2017: 26 · 2016: 27 · 2015: 2
- FWCI
- 9.03
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- pancreatic ductal adenocarcinoma, metabolite profiling, mesenchymal subtype, epithelial subtype, metabolic inhibitors, drug response prediction, glutamine metabolism, glucose metabolism, lipogenesis, mitochondrial function, redox homeostasis, cancer metabolism, pharmacogenomics, cancer cell lines
- MeSH terms
- Adenocarcinoma, Glucose, Glutamine, Glycolysis, Humans, Mesoderm, Transcription, Genetic, Biomarkers, Tumor, Reproducibility of Results, Inhibitory Concentration 50, Carcinoma, Pancreatic Ductal, Cell Proliferation, Lipogenesis, Metabolomics, Metabolome
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