The DOI matches its Crossref record; 59 of the 61 references it cites were found in a registry or an index.
Combination therapy with BPTES nanoparticles and metformin targets the metabolic heterogeneity of pancreatic cancer
Open accessAbstract
Significance: There are no effective therapies currently available for advanced pancreatic cancer. We show that there are two populations of cancer cells within a pancreatic tumor that require targeting by different metabolic inhibitors for effective tumor control. Rapidly dividing cells use glutamine, and can be effectively killed by administration of a nanoparticle containing an inhibitor of glutamine metabolism. Hypoxic cells, which are slowly dividing cells, metabolize glucose and can be targeted by metformin, a drug used for the treatment of diabetes. Clinical trials are needed to determine whether combination therapy, with drugs that effectively block the metabolism of glutamine and glucose, improves the survival of patients with pancreatic cancer.
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“pancreatic tumor-initiating cells have been found to preferentially utilize mitochondrial metabolism, as compared to glycolytic metabolism preferred by bulk tumor cells244.”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [244]
Citations
Cites
Rahib, L., Smith, B. D., Aizenberg, R., Rosenzweig, A. B., Fleshman, J. M., & Matrisian, L. M. (2014) · Cancer Research · doi:10.1158/0008-5472.can-14-0155 · Cited by 7,094
Core Signaling Pathways in Human Pancreatic Cancers Revealed by Global Genomic Analyses
Jones, S., Zhang, X., Parsons, D. W., Lin, J. C.-H., Leary, R. J., Angenendt, P., Mankoo, P., Carter, H., Kamiyama, H., Jimeno, A., et al. (2008) · Science · doi:10.1126/science.1164368 · Cited by 3,969
HMDB: the Human Metabolome Database
Wishart, D. S., Tzur, D., Knox, C., Eisner, R., Guo, A. C., Young, N., Cheng, D., Jewell, K., Arndt, D., Sawhney, S., et al. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkl923 · Cited by 3,219
From genomics to chemical genomics: new developments in KEGG
Kanehisa, M. I. (2005) · Nucleic Acids Research · doi:10.1093/nar/gkj102 · Cited by 3,126
OWEN, M. R., DORAN, E., & HALESTRAP, A. P. (2000) · Biochemical Journal · doi:10.1042/bj3480607 · Cited by 2,157
Wise, D. R., DeBerardinis, R. J., Mancuso, A., Sayed, N., Zhang, X.-Y., Pfeiffer, H. K., Nissim, I., Daikhin, E., Yudkoff, M., McMahon, S. B., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0810199105 · Cited by 2,001
Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway
Son, J., Lyssiotis, C. A., Ying, H., Wang, X., Hua, S., Ligorio, M., Perera, R. M., Ferrone, C. R., Mullarky, E., Shyh-Chang, N., et al. (2013) · Nature · doi:10.1038/nature12040 · Cited by 1,990
Inhibition of lactate dehydrogenase A induces oxidative stress and inhibits tumor progression
Le, A., Cooper, C. R., Gouw, A. M., Dinavahi, R., Maitra, A., Deck, L. M., Royer, R. E., Jagt, D. L. V., Semenza, G. L., & Dang, C. V. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0914433107 · Cited by 1,528
Self-citationEl-Mir, M.-Y., Nogueira, V., Fontaine, E., Avéret, N., Rigoulet, M., & Leverve, X. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.1.223 · Cited by 1,399
Reactome: a knowledgebase of biological pathways
Joshi-Tope, G. (2004) · Nucleic Acids Research · doi:10.1093/nar/gki072 · Cited by 1,291
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Pancreatic cancer: Advances and challenges
Halbrook, C. J., Lyssiotis, C. A., Pasca di Magliano, M., & Maitra, A. (2023) · Cell · doi:10.1016/j.cell.2023.02.014 · Cited by 1,321
Metabolism of Amino Acids in Cancer
Wei, Z. C., Liu, X., Cheng, C., Yu, W., & Yi, P. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.603837 · Cited by 456
Targeting hypoxic tumor microenvironment in pancreatic cancer
Tao, J., Yang, G., Zhou, W., Qiu, J., Chen, G., Luo, W., Zhao, F., You, L., Zheng, L., Zhang, T., et al. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-01030-w · Cited by 431
“Based on these observations, it was proposed that rapidly dividing cells use Gln, while hypoxic cells that are slowly dividing metabolize glucose [62].”
BackgroundEnergy metabolism in health and diseases
Liu, H., Wang, S., Wang, J., Guo, X., Song, Y., Fu, K., Gao, Z., Liu, D., He, W., & Yang, L. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02141-x · Cited by 484
Mitochondrial copper depletion suppresses triple-negative breast cancer in mice
Cui, L., Gouw, A. M., LaGory, E. L., Guo, S., Attarwala, N., Tang, Y., Qi, J., Chen, Y., Gao, Z., Casey, K. M., et al. (2020) · Nature Biotechnology · doi:10.1038/s41587-020-0707-9 · Cited by 347
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Metadata
- Authors
- Elgogary, A., Xu, Q., Poore, B., Alt, J., Zimmermann, S. C., Zhao, L., Fu, J., Chen, B., Xia, S., Liu, Y., Neisser, M., Nguyen, C., Lee, R., Park, J. K., Reyes, J., Hartung, T., Rojas, C., Rais, R., Tsukamoto, T., Semenza, G. L., Hanes, J., Slusher, B. S., & Le, A.
- Affiliations
- Johns Hopkins University (US)
- Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205;
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2016-08-24
- Volume
- 113
- Issue
- 36
- Pages
- E5328-36
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5018752
- OpenAlex
- W2515129893
- Cited by
- 234
- References
- 61
- Citations by year
- 2026: 16 · 2025: 20 · 2024: 17 · 2023: 25 · 2022: 24 · 2021: 38 · 2020: 32 · 2019: 19 · 2018: 21 · 2017: 21 · 2016: 1
- FWCI
- 8.61
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- HHS | NIH | National Cancer Institute (R01-CA193895, R21-CA169757)
- HHS | NIH | National Institute on Drug Abuse (R03-DA032470)
- HHS | NIH | National Institute of Mental Health (P30-MH075673)
- HHS | NIH | National Center for Advancing Translational Sciences (UL1-TR001079)
- 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 › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- BPTES, glutaminase inhibition, glutamine metabolism, pancreatic cancer, nanoparticles, drug encapsulation, metformin, combination therapy, tumor metabolic heterogeneity, tumor hypoxia, glycolysis, glycogen synthesis, CB-839, pharmacokinetics, cancer metabolism
- MeSH terms
- Animals, Antineoplastic Combined Chemotherapy Protocols, Glutaminase, Glutamine, Humans, Metformin, Pancreatic Neoplasms, Sulfides, Thiadiazoles, Proto-Oncogene Proteins p21(ras), Xenograft Model Antitumor Assays, Benzeneacetamides, Cell Line, Tumor, Mice, Nanoparticles
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