A landscape of metabolic variation across tumor types
Open accessAbstract
Tumor metabolism is reorganized to support proliferation in the face of growth-related stress. Unlike the widespread profiling of changes to metabolic enzyme levels in cancer, comparatively less attention has been paid to the substrates/products of enzyme-catalyzed reactions, small-molecule metabolites. We developed an informatic pipeline to concurrently analyze metabolomics data from over 900 tissue samples spanning seven cancer types, revealing extensive heterogeneity in metabolic changes relative to normal tissue across cancers of different tissues of origin. Despite this heterogeneity, a number of metabolites were recurrently differentially abundant across many cancers, such as lactate and acyl-carnitine species. Through joint analysis of metabolomic data alongside clinical features of patient samples, we also identified a small number of metabolites, including several polyamines and kynurenine, which were associated with aggressive tumors across several tumor types. Our findings offer a glimpse onto common patterns of metabolic reprogramming across cancers, and the work serves as a large-scale resource accessible via a web application (http://www.sanderlab.org/pancanmet).
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Elevated IDO1 and TDO activity and Kyn levels are associated with increased tumor grade and poor prognosis in many cancers.
“Elevated IDO1 and TDO activity and Kyn levels are associated with increased tumor grade and poor prognosis in many cancers. (28).”
From Reimagining IDO Pathway Inhibition in Cancer Immunotherapy via Downstream Focus on the Tryptophan–Kynurenine–Aryl Hydrocarbon Axis (2019) · cites this paper as [28]
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- Authors
- Reznik, E., Luna, A., Aksoy, B. A., Liu, E. M., La, K., Ostrovnaya, I., Creighton, C. J., Hakimi, A. A., & Sander, C.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Harvard University (US)
- Icahn School of Medicine at Mount Sinai (US)
- Weill Cornell Medicine (US)
- Baylor College of Medicine (US)
- Corresponding author
- Reznik, Ed
- Sander, Chris
- ORCID
- Venue
- Cell Systems
- Publisher
- Elsevier BV
- Published
- 2018-03
- Volume
- 6
- Issue
- 3
- Pages
- 301-313.e3
- ISSN
- 2405-4712 (ISSN-L)
- PMC
- PMC5876114
- OpenAlex
- W2785402763
- Cited by
- 172
- References
- 70
- Citations by year
- 2026: 10 · 2025: 15 · 2024: 27 · 2023: 22 · 2022: 24 · 2021: 29 · 2020: 15 · 2019: 24 · 2018: 6
- FWCI
- 5.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Systems (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (CA125123)
- National Cancer Institute (P30-CA008748)
- National Institute of General Medical Sciences (P41 GM103504)
- Israel National Road Safety Authority (F32 CA192901)
- Marie-Josée and Henry R. Kravis Center for Molecular Oncology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer and biochemical research
- Keywords
- cancer metabolism, tumor metabolic reprogramming, small molecule metabolites, lactate, acylcarnitines, polyamines, kynurenine, tumor aggressiveness, cancer metabolomics
- MeSH terms
- Algorithms, Humans, Neoplasms, Software, Computational Biology, Metabolomics
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