Cited by 398Cancer, Hypoxia, and MetabolismPancreatic and Hepatic Oncology ResearchCancer, Lipids, and Metabolism

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

Open access
Daemen, Anneleen, Peterson, David, Sahu, Nisebita, McCord, Ron, Du, Xiangnan, Liu, Bonnie, Kowanetz, Katarzyna, Hong, Rebecca +14 more·2015·Proceedings of the National Academy of Sciences

Abstract

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.

Integrity signals

Registry

Crossref · 10.1073/pnas.1501605112

Cites

60 of 60 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • 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]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

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)
Venue
Proceedings of the National Academy of Sciences
Published
2015-07-27
Volume
112
Issue
32
Pages
E4410-7
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
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
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review