Cited by 238Cancer, Hypoxia, and MetabolismPancreatic and Hepatic Oncology ResearchAmino Acid Enzymes and Metabolism

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Combination therapy with BPTES nanoparticles and metformin targets the metabolic heterogeneity of pancreatic cancer

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Elgogary, Amira, Xu, Qingguo, Poore, Brad, Alt, Jesse, Zimmermann, Sarah C., Zhao, Liang, Fu, Jie, Chen, Baiwei, Xia, Shiyu, Liu, Yanfei, Neisser, Marc, Nguyen, Christopher, Lee, Ramon, Park, Joshua K., Reyes, Juvenal, Hartung, Thomas, Rojas, Camilo, Rais, Rana, Tsukamoto, Takashi, Semenza, Gregg L., Hanes, Justin, Slusher, Barbara S., Le, Anne·2016·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.1611406113PMC PMC5018752

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Abstract

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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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: Xu, Qingguo
Poore, Brad
Alt, Jesse
Zhao, Liang
Fu, Jie
Xia, Shiyu
Liu, Yanfei
Nguyen, Christopher
Park, Joshua K.
Rojas, Camilo
Rais, Rana
Tsukamoto, Takashi
Semenza, Gregg L.
Hanes, Justin
Slusher, Barbara S.
Le, Anne
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
DOI: 10.1073/pnas.1611406113
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
Licence: www.pnas.org/preview_site/misc/userlicense.xhtml (vor)
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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Combination therapy with BPTES nanoparticles and metformin targets the metabolic heterogeneity of pancreatic cancer

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