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 preferentially utilize mitochondrial metabolism compared with the glycolytic metabolism preferred by bulk tumor cells.
“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]
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
OWEN, M. R., DORAN, E., & HALESTRAP, A. P. (2000) · Biochemical Journal · doi:10.1042/bj3480607 · Cited by 2,157 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Reactome: a knowledgebase of biological pathways
Joshi-Tope, G. (2004) · Nucleic Acids Research · doi:10.1093/nar/gki072 · Cited by 1,291 · see citing works
Evidence that glutamine, not sugar, is the major energy source for cultured HeLa cells.
Reitzer, L. J., Wice, B. M., & Kennell, D. (1979) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)30124-2 · Cited by 1,240 · see citing works
Hrkach, J. S., Hoff, D. D. V., Ali, M. M., Andrianova, E. A., Auer, J., Campbell, T., Witt, D. D., Figa, M. A., Figueiredo, M., Horhota, A. T., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3003651 · Cited by 1,147 · see citing works
Glucose-Independent Glutamine Metabolism via TCA Cycling for Proliferation and Survival in B Cells
Le, A., Lane, A. N., Hamaker, M., Bose, S., Gouw, A., Barbi, J., Tsukamoto, T., Rojas, C. J., Slusher, B. S., Zhang, H., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2011.12.009 · Cited by 1,095 · see citing works
Self-citationAntitumor activity of the glutaminase inhibitor CB-839 in triple-negative breast cancer
Gross, M. I., Demo, S. D., Dennison, J. B., Chen, L., Chernov-Rogan, T., Goyal, B., Janes, J. R., Laidig, G. J., Lewis, E. R., Li, J., et al. (2014) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-13-0870 · Cited by 1,068 · see citing works
Reactome knowledgebase of human biological pathways and processes
Matthews, L., Gopinath, G., Gillespie, M., Caudy, M., Croft, D., de Bono, B., Garapati, P., Hemish, J., Hermjakob, H., Jassal, B., et al. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkn863 · Cited by 873 · see citing works
KRAS: feeding pancreatic cancer proliferation
Bryant, K. L., Mancias, J. D., Kimmelman, A. C., & Der, C. J. (2014) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2013.12.004 · Cited by 675 · see citing works
Inhibition of Glutaminase Preferentially Slows Growth of Glioma Cells with Mutant IDH1
Seltzer, M. J., Bennett, B. D., Joshi, A. D., Gao, P., Thomas, A. G., Ferraris, D. V., Tsukamoto, T., Rojas, C. J., Slusher, B. S., Rabinowitz, J. D., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-1666 · Cited by 513 · see citing works
Self-citationComputational prediction of human metabolic pathways from the complete human genome
Romero, P. R., Wagg, J., GREEN, M. L., Kaiser, D., Krummenacker, M., & Karp, P. D. (2004) · Genome biology · doi:10.1186/gb-2004-6-1-r2 · Cited by 512 · see citing works
Fan, T. W. ‐., Lane, A. N., Higashi, R. M., Farag, M. A., Gao, H. T., Bousamra, M., & Miller, D. M. (2009) · Molecular Cancer · doi:10.1186/1476-4598-8-41 · Cited by 438 · see citing works
Metformin directly acts on mitochondria to alter cellular bioenergetics
Andrzejewski, S., Gravel, S., Pollak, M., & St‐Pierre, J. (2014) · Cancer & Metabolism · doi:10.1186/2049-3002-2-12 · Cited by 424 · see citing works
Guillaumond, F., Leca, J., Olivares, O., Lavaut, M.-N., Vidal, N., Berthezène, P., Dusetti, N. J., Loncle, C., Calvo, E., Turrini, O., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1219555110 · Cited by 413 · see citing works
Targeted inhibition of tumor-specific glutaminase diminishes cell-autonomous tumorigenesis
Xiang, Y., Stine, Z. E., Xia, J., Lu, Y., O’Connor, R. S., Altman, B. J., Hsieh, A. L., Gouw, A. M., Thomas, A. G., Gao, P., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci75836 · Cited by 409 · see citing works
Self-citationRoles for KRAS in Pancreatic Tumor Development and Progression
di Magliano, M. P., & Logsdon, C. D. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.01.071 · Cited by 397 · see citing works
Avgoustakis, K. (2004) · Current Drug Delivery · doi:10.2174/1567201043334605 · Cited by 382 · see citing works
Kisfalvi, K., Eibl, G., Sinnett‐Smith, J. W., & Rozengurt, E. (2009) · Cancer Research · doi:10.1158/0008-5472.can-09-0418 · Cited by 315 · see citing works
Cassago, A., Ferreira, A. P. S., Ferreira, I. M., Fornezari, C., Gomes, E. R. M., Greene, K. S., Pereira, H. M., Garratt, R. C., Dias, S. M. G., & Ambrosio, A. L. B. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1112495109 · Cited by 287 · see citing works
Jimeno, A., Feldmann, G., Suárez‐Gauthier, A., Rasheed, Z. A., Solomon, A., Zou, G.-M., Rubio‐Viqueira, B., García-García, E., López‐Ríos, F., Matsui, W. H., et al. (2009) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-08-0924 · Cited by 277 · see citing works
Feldmann, G., Fendrich, V., McGovern, K., Bedja, D., Bisht, S., Alvarez, H., Koorstra, J.-B. M., Habbe, N., Karikari, C. A., Mullendore, M. E., et al. (2008) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-08-0573 · Cited by 275 · see citing works
Yang, Q., Jones, S. W., Parker, C. L., Zamboni, W. C., Bear, J. E., & Lai, S. K. (2014) · Molecular Pharmaceutics · doi:10.1021/mp400703d · Cited by 273 · see citing works
Genetic Alterations and Oncogenic Pathways Associated with Breast Cancer Subtypes
Hu, X., Stern, H. M., Ge, L., O'Brien, C. L., Haydu, L. E., Honchell, C. D., Haverty, P. M., Peters, B. A., Wu, T. D., Amler, L. C., et al. (2009) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-08-0107 · Cited by 218 · see citing works
Thangavelu, K., Pan, C. Q., Karlberg, T., Balaji, G., Uttamchandani, M., Suresh, V., Schüler, H., Low, B. C., & Sivaraman, J. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1116573109 · Cited by 206 · see citing works
Pelletier, J., Bellot, G. L., Gounon, P., Lacas‐Gervais, S., Pouysségur, J., & Mazure, N. M. (2012) · Frontiers in Oncology · doi:10.3389/fonc.2012.00018 · Cited by 203 · see citing works
Shukla, K. H., Ferraris, D. V., Thomas, A. G., Stathis, M. J., Duvall, B. R., Delahanty, G., Alt, J., Rais, R., Rojas, C. J., Gao, P., et al. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm301191p · Cited by 199 · see citing works
Self-citationMarchiq, I., LeFloch, R., Roux, D., Simon, M., & Pouysségur, J. (2014) · Cancer Research · doi:10.1158/0008-5472.can-14-2260 · Cited by 175 · see citing works
Full-Length Human Glutaminase in Complex with an Allosteric Inhibitor
DeLaBarre, B., Größ, S., Fang, C., Gao, Y., Jha, A., Jiang, F., Juanhua Song, J., Wei, W., & Hurov, J. (2011) · Biochemistry · doi:10.1021/bi201613d · Cited by 159 · see citing works
Rajeshkumar, N. V., Dutta, P., Yabuuchi, S., de Wilde, R. F., Martinez, G. V., Le, A., Kamphorst, J. J., Rabinowitz, J. D., Jain, S. K., Hidalgo, M., et al. (2015) · Cancer Research · doi:10.1158/0008-5472.can-15-0108 · Cited by 158 · see citing works
Self-citationYabuuchi, S., Pai, S. G., Campbell, N. R., de Wilde, R. F., Oliveira, E. D., Korangath, P. C., Streppel, M. M., Rasheed, Z. A., Hidalgo, M. M., Maitra, A., et al. (2013) · Cancer Letters · doi:10.1016/j.canlet.2013.01.054 · Cited by 140 · see citing works
Torres, M. P., Rachagani, S., Souchek, J. J., Mallya, K. B., Johansson, S. L., & Batra, S. K. (2013) · PLoS ONE · doi:10.1371/journal.pone.0080580 · Cited by 137 · see citing works
Effect of Metformin vs Placebo on and Metabolic Factors in NCIC CTG MA.32
Goodwin, P. J., Parulekar, W. R., Gelmon, K. A., Shepherd, L. E., Ligibel, J. A., Hershman, D. L., Rastogi, P., Mayer, I. A., Hobday, T. J., Lemieux, J., et al. (2015) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djv006 · Cited by 130 · see citing works
Self-citationIsotopomer‐Based Metabolomic Analysis by NMR and Mass Spectrometry
Lane, A. N., Fan, T. W. ‐., & Higashi, R. M. (2007) · Methods in cell biology · doi:10.1016/s0091-679x(07)84018-0 · Cited by 123 · see citing works
Scalable method to produce biodegradable nanoparticles that rapidly penetrate human mucus
Xu, Q., Boylan, N. J., Cai, S., Miao, B., Patel, H., & Hanes, J. S. (2013) · Journal of Controlled Release · doi:10.1016/j.jconrel.2013.05.035 · Cited by 122 · see citing works
Self-citationGenome profiling of pancreatic adenocarcinoma
Birnbaum, D. J., Adélaïde, J., Mamessier, E., Finetti, P., Lagarde, A., Monges, G., Viret, F., Gonçalvès, A., Turrini, O., Delpero, J., et al. (2011) · Genes, Chromosomes and Cancer · doi:10.1002/gcc.20870 · Cited by 122 · see citing works
NMR-based stable isotope resolved metabolomics in systems biochemistry
Fan, T. W. ‐., & Lane, A. N. (2011) · Journal of Biomolecular NMR · doi:10.1007/s10858-011-9484-6 · Cited by 119 · see citing works
Stable isotope resolved metabolomics of lung cancer in a SCID mouse model
Fan, T. W. ‐., Lane, A. N., Higashi, R. M., & Yan, J. (2010) · Metabolomics · doi:10.1007/s11306-010-0249-0 · Cited by 115 · see citing works
Moseley, H. (2010) · BMC Bioinformatics · doi:10.1186/1471-2105-11-139 · Cited by 101 · see citing works
Metformin inhibits renal cell carcinoma in vitro and in vivo xenograft
Liu, J., Li, M., Song, B., Jia, C., Zhang, L., Bai, X., & Wei-lie, H. (2011) · Urologic Oncology Seminars and Original Investigations · doi:10.1016/j.urolonc.2011.01.003 · Cited by 96 · see citing works
Isotopomer analysis of lipid biosynthesis by high resolution mass spectrometry and NMR
Lane, A. N., Fan, T. W. ‐., Xie, Z., Moseley, H., & Higashi, R. M. (2009) · Analytica Chimica Acta · doi:10.1016/j.aca.2009.08.032 · Cited by 90 · see citing works
Metformin Inhibits the Growth of Human Pancreatic Cancer Xenografts
Kisfalvi, K., Moro, A., Sinnett‐Smith, J. W., Eibl, G., & Rozengurt, E. (2013) · Pancreas · doi:10.1097/mpa.0b013e31827aec40 · Cited by 86 · see citing works
Walters, D. M., Stokes, J. B., Adair, S. J., Stelow, E. B., Borgman, C. A., Lowrey, B. T., Xin, W., Blais, E. M., Lee, J. K., Papin, J. A., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0077065 · Cited by 76 · see citing works
Kinetic characterization of ebselen, chelerythrine and apomorphine as glutaminase inhibitors
Thomas, A. G., Rojas, C. J., Tanega, C., Shen, M., Simeonov, A. M., Boxer, M. B., Auld, D. S., Ferraris, D. V., Tsukamoto, T., & Slusher, B. S. (2013) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2013.06.110 · Cited by 75 · see citing works
Self-citationAllosteric Glutaminase Inhibitors Based on a 1,4-Di(5-amino-1,3,4-thiadiazol-2-yl)butane Scaffold
Zimmermann, S. C., Wolf, E. F., Luu, A., Thomas, A. G., Stathis, M. J., Poore, B., Nguyen, C. C., Le, A., Rojas, C. J., Slusher, B. S., et al. (2016) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.6b00060 · Cited by 68 · see citing works
Self-citationFive Primary Human Pancreatic Adenocarcinoma Cell Lines Established by the Outgrowth Method
Rückert, F., Aust, D., Böhme, I., Werner, K., Brandt, A., Diamandis, E. P., Krautz, C., Hering, S., Saeger, H., Grützmann, R., et al. (2011) · Journal of Surgical Research · doi:10.1016/j.jss.2011.04.021 · Cited by 63 · see citing works
Tumorigenicity of hypoxic respiring cancer cells revealed by a hypoxia–cell cycle dual reporter
Le, A., Stine, Z. E., Nguyen, C. C., Afzal, J. M., Sun, P., Hamaker, M. C., Siegel, N. M., Gouw, A. M., Kang, B.-H., Yu, S.-H., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1402012111 · Cited by 58 · see citing works
Self-citationHarding, J. J., Telli, M. L., Münster, P. N., Le, M. H., Molineaux, C. J., Bennett, M. K., Mittra, E., Burris, H. A., Clark, A. S., Dunphy, M. P., et al. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2015.33.15_suppl.2512 · Cited by 58 · see citing works
Phase I study and clinical pharmacology of 6-diazo-5-oxo-L-norleucine (DON)
Rahman, A., Smith, F. P., Luc, P.-V. T., & Woolley, P. V. (1985) · Investigational New Drugs · doi:10.1007/bf00170760 · Cited by 49 · see citing works
Fan, T. W. ‐., Tan, J., McKinney, M. M., & Lane, A. N. (2011) · Metabolomics · doi:10.1007/s11306-011-0337-9 · Cited by 45 · see citing works
Blackwood, E. R., Epler, J., Yen, I., Flagella, M., O'Brien, T., Evangelista, M., Schmidt, S., Xiao, Y., Choi, J. D., Kowanetz, K., et al. (2013) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-12-1218 · Cited by 37 · see citing works
Preview of Hawaii Cancer Facts and Figures 2010.
Hernandez, B. Y., Green, M. D., Cassel, K., Pobutsky, A., Vu, V., & Wilkens, L. R. (2010) · PubMed Central · Cited by 34 · see citing works
Construction of orthotopic xenograft mouse models for human pancreatic cancer
Dai, L., Lu, C., Yu, X., Dai, L., & Zhou, J. X. (2015) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2015.2642 · Cited by 26 · see citing works
Flagged first, then by citations
2 of the 61 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
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 · see citing works
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 439 · see citing works
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 419 · see citing works
“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 438 · see citing works
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 346 · see citing works
Self-citationTargeting mitochondrial metabolism for precision medicine in cancer
Sainero‐Alcolado, L., Liaño-Pons, J., Ruiz-Pérez, M. V., & Arsenian‐Henriksson, M. (2022) · Cell Death and Differentiation · doi:10.1038/s41418-022-01022-y · Cited by 330 · see citing works
“Genetic silencing or the inhibition of glutaminase (GLS) using the allosteric inhibitor BPTES [93] decreases proliferation, induces cell death, and reduces proliferation in cancer cell lines as well as tumor growth in vivo [94, 95].”
Compensatory metabolic networks in pancreatic cancers upon perturbation of glutamine metabolism
Biancur, D. E., Paulo, J. A., Małachowska, B., Quiles Del Rey, M., Sousa, C. M., Wang, X., Sohn, A. S. W., Chu, G. C., Gygi, S. P., Harper, J. W., et al. (2017) · Nature Communications · doi:10.1038/ncomms15965 · Cited by 315 · see citing works
Tumor microenvironment targeted nanotherapeutics for cancer therapy and diagnosis: A review
Thakkar, S., Sharma, D., Kalia, K., & Tekade, R. K. (2019) · Acta Biomaterialia · doi:10.1016/j.actbio.2019.09.009 · Cited by 317 · see citing works
Muir, A., Danai, L. V., Gui, D. Y., Waingarten, C. Y., Lewis, C. A., & Vander Heiden, M. G. (2017) · eLife · doi:10.7554/elife.27713 · Cited by 311 · see citing works
“…into glutamate and downstream metabolites during a presteady state, kinetic labeling period and this method has previously been used to corroborate predicted changes in tumor glutamine utilization (Elgogary et al., 2016; Lane et al., 2015; Tardito et al., 2015; Yuneva et al., 2012) (Figure 5B).”
MethodGluconeogenesis in Cancer: Function and Regulation of PEPCK, FBPase, and G6Pase
Wang, Z., & Dong, C. (2018) · Trends in cancer · doi:10.1016/j.trecan.2018.11.003 · Cited by 294 · see citing works
Metabolic reprogramming in cancer: Mechanisms and therapeutics
Nong, S., Han, X., Yu, X., Qian, Y., Wei, Y., Zhang, T., Tian, K., Shen, K., Yang, J., & Ma, X. (2023) · MedComm · doi:10.1002/mco2.218 · Cited by 300 · see citing works
Sharifi-Rad, J., Quispe, C., Butnariu, M., Rotariu, L. S., Sytar, O., Sestito, S., Rapposelli, S., Akram, M., Iqbal, M., Krishna, A., et al. (2021) · Cancer Cell International · doi:10.1186/s12935-021-02025-4 · Cited by 290 · see citing works
“For example, nanoparticles with the antidiabetic drug metformin have been shown to be effective in a pancreatic cancer cell population by inhibiting glutamine metabolism [13].”
BackgroundTan, Z., Xiao, L., Tang, M., Bai, F., Li, J., Li, L., Shi, F., Li, N., Li, Y., Du, Q., et al. (2018) · Theranostics · doi:10.7150/thno.21451 · Cited by 272 · see citing works
“Integrative metabolomics analysis was applied to discover the adaptive nutrients usage and specific metabolic pathway-addition in metformin-tolerant ovarian cancer and KRASablation-resistant pancreatic cancer [68-70].”
MethodAmino Acid Depletion Therapies: Starving Cancer Cells to Death
Butler, M., van der Meer, L. T., & van Leeuwen, F. N. (2021) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2021.03.003 · Cited by 269 · see citing works
“To increase the half-life and reduce immunogenicity, therapeutic enzymes have been modified by conjugation to polyethylene glycol (PEG) [96], nanoparticle encapsulation [78], or erythrocyte encapsulation [97], and the treatment can be combined with immune-suppressive agents such as prednisone and dexamethasone.”
BackgroundLi, B., Cao, Y., Meng, G., Qian, L., Xu, T., Yan, C., Luo, O., Wang, S., Wei, J., Ding, Y., et al. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2018.11.063 · Cited by 245 · see citing works
Glutamine Metabolism in Cancer
Li, T., & Le, A. (2018) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-77736-8_2 · Cited by 240 · see citing works
Self-citationWe're Not “DON” Yet: Optimal Dosing and Prodrug Delivery of6-Diazo-5-oxo-L-norleucine
Lemberg, K. M., Vornov, J. J., Rais, R., & Slusher, B. S. (2018) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-17-1148 · Cited by 238 · see citing works
“2A) were designed to introduce bulky hydrophobic groups to enhance the cLogP and cellular permeability of DON, while maintaining plasma stability such that the peripheral exposure to DON would be limited (11, 58).”
BackgroundSelf-citationLi, Y., Lih, T. M., Dhanasekaran, S. M., Mannan, R., Chen, L., Cieslik, M. P., Wu, Y., Lu, R. J.-H., Clark, D. J., Kołodziejczak, I., et al. (2022) · Cancer Cell · doi:10.1016/j.ccell.2022.12.001 · Cited by 229 · see citing works
Self-citationGlucose Metabolism in Cancer: The Warburg Effect and Beyond
Bose, S., Zhang, C., & Le, A. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-65768-0_1 · Cited by 226 · see citing works
Self-citationWang, Z., Liu, F., Fan, N., Zhou, C., Li, D., MacVicar, T., Dong, Q., Bruns, C. J., & Zhao, Y. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.589508 · Cited by 184 · see citing works
“Several inhibitors targeting glycolysis have demonstrated a synergistic effect with glutaminase inhibitor, such as metformin (115, 143, 144), Erlotinib (EGFR inhibitor) (145), MLN128 (mTOR inhibitor) (52), and Glutor (glucose uptake inhibitor) (146).”
BackgroundDrug-induced amino acid deprivation as strategy for cancer therapy
Fung, M. K. L., & Chan, G. (2017) · Journal of Hematology & Oncology · doi:10.1186/s13045-017-0509-9 · Cited by 172 · see citing works
“Recent development of a novel BPTES formulation, the BPTES nanoparticles (BPTES-NPs) were reported to have anti-tumor activity comparable to CB-839 in an orthotopic pancreatic cancer mouse model [61].”
BackgroundMethodInfluentialGe, J., Cui, H., Xie, N., Banerjee, S., Guo, S., Dubey, S., Barnes, S., & Liu, G. (2018) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2017-0238oc · Cited by 166 · see citing works
“In addition, we applied glutamine deprivation to dampen glutaminolysis and found that, similarly to CB-839 and BPTES, this procedure decreased only collagen I and collagen III in myofibroblasts (Figure 2F).”
InfluentialWang, Y.-Q., Wang, H.-L., Xu, J., Tan, J., Fu, L., Wang, J., Zou, T., Sun, D., Gao, Q., Chen, Y., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-02951-4 · Cited by 169 · see citing works
Therapeutic targeting of glutaminolysis as an essential strategy to combat cancer
Matés, J. M., Paola, F. J. D., Campos-Sandoval, J. A., Mazurek, S., & Márquez, J. (2019) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2019.05.012 · Cited by 164 · see citing works
Lipid Metabolism and Lipid Droplets in Pancreatic Cancer and Stellate Cells
Sunami, Y., Rebelo, A., & Kleeff, J. H. (2017) · Cancers · doi:10.3390/cancers10010003 · Cited by 154 · see citing works
Simón, J., Núñez-García, M., Fernández-Tussy, P., Barbier-Torres, L., Fernández-Ramos, D., Gómez-Santos, B., Buqué, X., Lopitz-Otsoa, F., Goikoetxea-Usandizaga, N., Serrano-Maciá, M., et al. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.01.013 · Cited by 141 · see citing works
“, 2012), BPTES-loaded polyethylenoglycol nanoparticles, a nanoencapsulation allowing the safe administration of this drug, are currently being tested in pre-clinical mouse models (Elgogary et al., 2016).”
BackgroundDiabetes Mellitus and Obesity as Risk Factors for Pancreatic Cancer
Eibl, G., Cruz‐Monserrate, Z., Korc, M., Petrov, M. S., Goodarzi, M. O., Fisher, W. E., Habtezion, A., Lugea, A., Pandol, S. J., Hart, P. A., et al. (2017) · Journal of the Academy of Nutrition and Dietetics · doi:10.1016/j.jand.2017.07.005 · Cited by 138 · see citing works
Timbie, K. F., Afzal, U., Date, A. A., Zhang, C., Song, J. S., Miller, G. W., Suk, J. S., Hanes, J. S., & Price, R. J. (2017) · Journal of Controlled Release · doi:10.1016/j.jconrel.2017.03.017 · Cited by 131 · see citing works
Self-citationZhao, Y., Feng, X., Chen, Y., Selfridge, J. E., Gorityala, S., Du, Z., Wang, J. M., Hao, Y., Cioffi, G., Conlon, R. A., et al. (2020) · Cancer Research · doi:10.1158/0008-5472.can-20-0600 · Cited by 130 · see citing works
Zhong, G., Su, S., Li, J., Zhao, H., Hu, D., Chen, J., Li, S., Lin, Y., Wen, L., Lin, X., et al. (2023) · Science Advances · doi:10.1126/sciadv.adg0478 · Cited by 127 · see citing works
Pancreatic Cancer: Molecular Characterization, Clonal Evolution and Cancer Stem Cells
Pelosi, E., Castelli, G., & Testa, U. (2017) · Biomedicines · doi:10.3390/biomedicines5040065 · Cited by 124 · see citing works
“Furthermore, glutaminase inhibitors sensitize pancreatic cancer cells to PARP-driven cytotoxic effects on PDAC cells [240].”
BackgroundTranscriptional factor ICER promotes glutaminolysis and the generation of Th17 cells
Kono, M., Yoshida, N., Maeda, K., & Tsokos, G. C. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1714717115 · Cited by 121 · see citing works
“At the translational level, Gls1 inhibitors are being considered for the treatment of various cancers in mice (28, 29), and some of them have entered clinical trials (17, 30).”
BackgroundGlutamine Metabolism in Cancer
Li, T., Copeland, C., & Le, A. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-65768-0_2 · Cited by 130 · see citing works
Self-citationGLS1-mediated glutaminolysis unbridled by MALT1 protease promotes psoriasis pathogenesis
Xia, X., Cao, G., Sun, G., Zhu, L., Tian, Y., Song, Y., Guo, C., Wang, X., Zhong, J., Zhou, W., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci129269 · Cited by 120 · see citing works
“GLS1 inhibitors are being considered for the treatment of various cancers in mice (55, 56), and some of them have entered clinical trials (57, 58).”
BackgroundKono, M., Yoshida, N., Maeda, K., Suárez‐Fueyo, A., Kyttaris, V. C., & Tsokos, G. C. (2019) · Arthritis & Rheumatology · doi:10.1002/art.41019 · Cited by 116 · see citing works
“Gls1 inhibitors have been considered for the treatment of various cancers in mice (23,24), and some of them have entered clinical trials (25,26).”
BackgroundHIV infection and latency induce a unique metabolic signature in human macrophages
Castellano, P., Prevedel, L., Valdebenito, S., & Eugenín, E. A. (2019) · Scientific Reports · doi:10.1038/s41598-019-39898-5 · Cited by 109 · see citing works
Combination of metformin with chemotherapeutic drugs via different molecular mechanisms
Peng, M., Darko, K. O., Tao, T., Huang, Y., Su, Q., He, C., Yin, T., Liu, Z., & Yang, X. (2017) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2017.01.005 · Cited by 111 · see citing works
Uncovering the Role of N-Acetyl-Aspartyl-Glutamate as a Glutamate Reservoir in Cancer
Nguyen, T. A., Kirsch, B. J., Asaka, R., Nabi, K., Quinones, A., Tan, J., Antonio, M. J., Camelo, F., Li, T., Nguyen, S. A., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.03.036 · Cited by 111 · see citing works
“Lower cell numbers and glutamate concentrations in the shGCPII-KD cells treated with BPTES compared to those in shControl treated with BPTES demonstrate a growth advantage when cells have GCPII to partially compensate for the decrease in glutamate caused by glutaminase inhibition.”
BackgroundMethodInfluentialSelf-citationBoysen, G., Jamshidi‐Parsian, A., Davis, M. A., Siegel, E. R., Simecka, C. M., Kore, R. A., Dings, R. P. M., & Griffin, R. J. (2018) · International Journal of Radiation Biology · doi:10.1080/09553002.2018.1558299 · Cited by 107 · see citing works
“To overcome this limitation, Elgogary et al. (2016) demonstrate the improved pharmacokinetics and efficacy of BPTES bound to nanoparticles compared with free BPTES.”
BackgroundQie, S., Yoshida, A., Parnham, S. R., Oleinik, N. V., Beeson, G. C., Beeson, C. C., Öğretmen, B., Bass, A. J., Wong, K., Rustgi, A. K., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09179-w · Cited by 101 · see citing works
Soth, M., Le, K., Francesco, M. E. D., Hamilton, M. M., Liu, G., Burke, J. P., Carroll, C. L., Kovacs, J. J., Bardenhagen, J., Bristow, C. A., et al. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01398 · Cited by 102 · see citing works
Glutaminase-1 (GLS1) inhibition limits metastatic progression in osteosarcoma
Ren, L., Ruiz‐Rodado, V., Dowdy, T., Huang, S., Issaq, S. H., Beck, J. A., Wang, H., Hoang, C. D., Lita, A., Larion, M., et al. (2020) · Cancer & Metabolism · doi:10.1186/s40170-020-0209-8 · Cited by 102 · see citing works
Jiang, Q., Qiu, Y., Kurland, I. J., Drlica, K., Subbian, S., Tyagi, S., & Shi, L. (2022) · mBio · doi:10.1128/mbio.01274-22 · Cited by 98 · see citing works
Glutaminase isoenzymes in the metabolic therapy of cancer
Matés, J. M., Campos-Sandoval, J. A., & Márquez, J. (2018) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2018.07.007 · Cited by 97 · see citing works
Lessons Learned from Two Decades of Anticancer Drugs
Liu, Z., Delavan, B., Roberts, R. A., & Tong, W. (2017) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2017.06.005 · Cited by 95 · see citing works
Metabolic heterogeneity and plasticity of glioma stem cells in a mouse glioblastoma model
Shibao, S., Minami, N., Koike, N., Fukui, N., Yoshida, K., Saya, H., & Sampetrean, O. (2017) · Neuro-Oncology · doi:10.1093/neuonc/nox170 · Cited by 89 · see citing works
Chen, Z., Li, D., Xu, N., Fang, J., Yu, Y., Hou, W., Ruan, H., Zhu, P., Ma, R., Lu, S., et al. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b01198 · Cited by 91 · see citing works
Endothelial Cell Glucose Metabolism and Angiogenesis
Du, W., Ren, L., Hamblin, M. H., & Fan, Y. (2021) · Biomedicines · doi:10.3390/biomedicines9020147 · Cited by 92 · see citing works
“GLS1 6 BPTES CB-839 Osteosarcoma, pancreatic cancer Multiple cancers Preclinical [114,115] Clinical phase I/II [32]”
BackgroundTargeting GLS1 to cancer therapy through glutamine metabolism
Yu, W., Yang, X., Zhang, Q., Sun, L., Yuan, S., & Xin, Y. (2021) · Clinical & Translational Oncology · doi:10.1007/s12094-021-02645-2 · Cited by 86 · see citing works
Nanomaterial-based regulation of redox metabolism for enhancing cancer therapy
Jia, X., Wang, Y., Qiao, Y., Jiang, X., & Li, J. (2024) · Chemical Society Reviews · doi:10.1039/d4cs00404c · Cited by 87 · see citing works
Liang, G., Cao, W., Tang, D., Zhang, H., Yu, Y., Ding, J., Karges, J., & Xiao, H. (2024) · ACS Nano · doi:10.1021/acsnano.3c11154 · Cited by 88 · see citing works
Metabolomics in drug research and development: The recent advances in technologies and applications
Pang, H., & Hu, Z. (2023) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2023.05.021 · Cited by 87 · see citing works
Halbrook, C. J., Thurston, G., Boyer, S., Anaraki, C., Jiménez, J. A., McCarthy, A., Steele, N. G., Kerk, S. A., Hong, H. S., Lin, L., et al. (2022) · Nature Cancer · doi:10.1038/s43018-022-00463-1 · Cited by 80 · see citing works
Phytonanotherapy for management of diabetes using green synthesis nanoparticles
Anand, K., Tiloke, C., Naidoo, P., & Chuturgoon, A. A. (2017) · Journal of Photochemistry and Photobiology B Biology · doi:10.1016/j.jphotobiol.2017.06.028 · Cited by 80 · see citing works
“Taking this into account these investigators combined metformin and the aforementioned nanoparticle therapy together and found a significant reduction in tumour growth (Elgogary et al., 2016).”
BackgroundThe Heterogeneity of Lipid Metabolism in Cancer
Park, J. K., Coffey, N. J., Limoges, A., & Le, A. (2018) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-77736-8_3 · Cited by 79 · see citing works
Self-citationTargeting Glutamine Metabolism to Enhance Immunoprevention of EGFR‐Driven Lung Cancer
Huang, M., Xiong, D., Pan, J., Zhang, Q., Sei, S., Shoemaker, R. H., Lubet, R. A., Montuenga, L. M., Wang, Y., Slusher, B. S., et al. (2022) · Advanced Science · doi:10.1002/advs.202105885 · Cited by 77 · see citing works
Self-citationTarannum, M., & Vivero-Escoto, J. L. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114357 · Cited by 77 · see citing works
Xu, R., Yang, J., Ren, B., Wang, H., Yang, G., Chen, Y., You, L., & Zhao, Y. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.572722 · Cited by 70 · see citing works
Application of metabolomics technologies toward cancer prognosis and therapy
Hoang, G., Udupa, S., & Le, A. (2019) · International review of cytology · doi:10.1016/bs.ircmb.2019.07.003 · Cited by 73 · see citing works
Self-citationInhibition of glutaminolysis in combination with other therapies to improve cancer treatment
Shen, Y., Chen, C., Huang, Y., Evans, E. E., Cheng, C., Chuang, Y.-J., Zhang, C., & Le, A. (2021) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2021.01.006 · Cited by 73 · see citing works
Self-citationBukhari, S. N. A. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14040866 · Cited by 74 · see citing works
Tao, H., Zhong, X., Zeng, A., & Song, L. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1208870 · Cited by 73 · see citing works
Targeting KRAS: from metabolic regulation to cancer treatment
Shi, Y., Zheng, H., Wang, T., Zhou, S., Zhao, S., Li, M., & Cao, B. (2025) · Molecular Cancer · doi:10.1186/s12943-024-02216-3 · Cited by 75 · see citing works
“Another GLS1 inhibitor BPTES also faces challenges; although it shows promising anti-tumor effects against KRAS-mutant pancreatic cancer, its poor water solubility limits its further application [70–73].”
Xu, L., Xu, R. F., Saw, P. E., Wu, J., Cheng, S., & Xu, X. (2021) · Nano Letters · doi:10.1021/acs.nanolett.1c02073 · Cited by 69 · see citing works
Hoerner, C. R., Chen, V. J., & Fan, A. C. (2019) · Kidney Cancer · doi:10.3233/kca-180043 · Cited by 68 · see citing works
“The availability of structural information about these drugs in complex with GLS1 has led to efforts to rationally evolve BPTES into more potent and stable analogues with better solubility.”
InfluentialMetabolic heterogeneity in cancer: An overview and therapeutic implications
Yu, T., Gao, W., & Liu, Y. (2020) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2020.188421 · Cited by 66 · see citing works
Self-citationTherapeutic Repurposing of Biguanides in Cancer
Zhao, H., Swanson, K. D., & Zheng, B. (2021) · Trends in cancer · doi:10.1016/j.trecan.2021.03.001 · Cited by 65 · see citing works
Metabolic reprogramming and interventions in angiogenesis
Liu, Y., Wu, Z., Li, Y., Chen, Y., Zhao, X., Wu, M., & Xia, Y. (2024) · Journal of Advanced Research · doi:10.1016/j.jare.2024.05.001 · Cited by 68 · see citing works
“In breast cancer and pancreatic cancer, BPTES has efficacy in regulating the metabolism of cancer cells and reducing the tumor growth in mouse model, which is as an irreversible allosteric inhibitor of GLS1 [169,170].”
Self-citationInhibition of Karyopherin beta 1 suppresses prostate cancer growth
Yang, J., Guo, Y., Lu, C., Zhang, R., Wang, Y. E., Luo, L., Zhang, Y., Chu, C. H., Wang, K. J., Obbad, S. I., et al. (2019) · Oncogene · doi:10.1038/s41388-019-0745-2 · Cited by 64 · see citing works
Dual regulation of mitochondrial fusion by Parkin–PINK1 and OMA1
Yamada, T., Ikeda, A., Murata, D., Wang, H., Zhang, C., Khare, P., Adachi, Y., Ito, F., Quirós, P. M., Blackshaw, S., et al. (2025) · Nature · doi:10.1038/s41586-025-08590-2 · Cited by 63 · see citing works
Self-citationUdupa, S., Nguyen, S. A., Hoang, G., Nguyen, T. A., Quinones, A., Pham, K., Asaka, R., Nguyen, K., Zhang, C., Elgogary, A., et al. (2019) · PROTEOMICS · doi:10.1002/pmic.201800451 · Cited by 63 · see citing works
Self-citationBioenergetic Metabolism In Osteoblast Differentiation
Shen, L., Hu, G., & Karner, C. M. (2022) · Current Osteoporosis Reports · doi:10.1007/s11914-022-00721-2 · Cited by 62 · see citing works
Targeting cellular metabolism to reduce head and neck cancer growth
Yang, J., Guo, Y., Seo, W., Zhang, R., Lu, C., Wang, Y. E., Luo, L., Paul, B., Yan, W., Saxena, D. B., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-41523-4 · Cited by 63 · see citing works
Colorectal cancers utilize glutamine as an anaplerotic substrate of the TCA cycle in vivo
Zhao, Y., Zhao, X., Chen, V., Feng, Y., Wang, L., Croniger, C. M., Conlon, R. A., Markowitz, S. D., Fearon, E. R., Puchowicz, M., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-55718-2 · Cited by 61 · see citing works
Recent Progress in the Discovery of Allosteric Inhibitors of Kidney-Type Glutaminase
Zimmermann, S. C., Duvall, B. R., & Tsukamoto, T. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b00327 · Cited by 59 · see citing works
Self-citationDeveloping New Cancer Nanomedicines by Repurposing Old Drugs
Yang, B., & Shi, J. (2020) · Angewandte Chemie International Edition · doi:10.1002/anie.202004317 · Cited by 60 · see citing works
The Metabolic Heterogeneity and Flexibility of Cancer Stem Cells
Tanabe, A., & Sahara, H. (2020) · Cancers · doi:10.3390/cancers12102780 · Cited by 59 · see citing works
Ajoolabady, A., Aghanejad, A., Bi, Y., Zhang, Y., Aslkhodapasandhukmabad, H., Abhari, A., & Ren, J. T. (2020) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2020.188366 · Cited by 57 · see citing works
Greene, M. K., Johnston, M. C., & Scott, C. J. (2021) · Cancers · doi:10.3390/cancers13246175 · Cited by 56 · see citing works
Dai, W., Ruan, C., Sun, Y., Gao, X., & Liang, J. (2020) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2020.110802 · Cited by 56 · see citing works
LKB1 promotes metabolic flexibility in response to energy stress
Parker, S. J., Svensson, R. U., Divakaruni, A. S., Lefebvre, A. E. Y. T., Murphy, A. N., Shaw, R. J., & Metallo, C. M. (2016) · Metabolic Engineering · doi:10.1016/j.ymben.2016.12.010 · Cited by 52 · see citing works
“Furthermore, a more recent study aimed at improving the pharmacokinetics of BPTES by loading into PLGA-PEG nanoparticles (BPTESNP) reported synergistic effects of BPTES-NP and metformin treatment in orthotopic models of pancreatic cancer (Elgogary et al., 2016).”
BackgroundSingleton, D. C., Dechaume, A.-L., Murray, P. M., Katt, W. P., Baguley, B. C., & Leung, E. Y. (2020) · BMC Cancer · doi:10.1186/s12885-020-06885-3 · Cited by 54 · see citing works
The Heterogeneity of Liver Cancer Metabolism
Salazar, J., & Le, A. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-65768-0_9 · Cited by 54 · see citing works
Self-citationLuo, Z., Xu, J., Sun, J., Huang, H., Zhang, Z., Ma, W., Wan, Z., Liu, Y., Pardeshi, A., & Li, S. (2020) · Acta Biomaterialia · doi:10.1016/j.actbio.2020.01.019 · Cited by 50 · see citing works
“One possible reason is that the complicated metabolic network in cancer provides a mechanism of compensation when one metabolic pathway is inhibited [28, 48].”
BackgroundSelf-citationTargeting glycolysis for cancer therapy using drug delivery systems
Huang, Y. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.12.003 · Cited by 51 · see citing works
Genetically Programmable Vesicles for Enhancing CAR‐T Therapy against Solid Tumors
Li, X., Zhu, T., Wang, R., Chen, J., Tang, L., Huo, W., Huang, X., & Cao, Q. (2023) · Advanced Materials · doi:10.1002/adma.202211138 · Cited by 48 · see citing works
Comprehensive proteogenomic characterization of rare kidney tumors
Li, G. X., Chen, L., Hsiao, Y., Mannan, R., Zhang, Y., Luo, J., Petralia, F., Cho, H., Hosseini, N., Leprevost, F. D. V., et al. (2024) · Cell Reports Medicine · doi:10.1016/j.xcrm.2024.101547 · Cited by 48 · see citing works
Self-citationNguyen, T., Le, N. Q. K., Ho, Q., Phan, D., & Ou, Y. (2019) · Analytical Biochemistry · doi:10.1016/j.ab.2019.04.011 · Cited by 45 · see citing works
The Metabolic Interplay between Cancer and Other Diseases
Le, A., Udupa, S., & Zhang, C. (2019) · Trends in cancer · doi:10.1016/j.trecan.2019.10.012 · Cited by 48 · see citing works
Self-citationTumor microenvironment-regulating nanomedicine design to fight multi-drug resistant tumors.
Xu, Q.-Q., Lan, X., Lin, H.-W., Xi, Q., Wang, M., Quan, X.-L., Yao, G.-Y., Yu, Z.-Q., Wang, Y.-X., & Yu, M. (2022) · Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology · doi:10.1002/wnan.1842 · Cited by 36 · see citing works
Self-citationJin, X., Zhang, S., Liang, J., Zhang, S. Y., Qin, Y., Huang, Q., Liu, C., & Zhang, X. (2023) · Advanced Materials · doi:10.1002/adma.202309094 · Cited by 44 · see citing works
Glutamine Metabolism: Molecular Regulation, Biological Functions, and Diseases
Kumar, M. A., Baba, S. K., Khan, I. R., Khan, M. S., Husain, F. M., Ahmad, S., Haris, M., Singh, M., Akil, A. A., Macha, M. A., et al. (2025) · MedComm · doi:10.1002/mco2.70120 · Cited by 49 · see citing works
Zhu, M., Fang, J., Zhang, J., Zhang, Z., Xie, J., Yu, Y., Ruan, J. J., Chen, Z., Hou, W., Yang, G., et al. (2017) · Analytical Chemistry · doi:10.1021/acs.analchem.6b03849 · Cited by 44 · see citing works
Self‐Delivery Nanomedicine for Glutamine‐Starvation Enhanced Photodynamic Tumor Therapy
Zhao, L., Chen, S., Zheng, R., Kong, R., Rao, X., Chen, A., Cheng, H. B., Zhang, D., Li, S., & Yu, X. (2021) · Advanced Healthcare Materials · doi:10.1002/adhm.202102038 · Cited by 43 · see citing works
Self-citationBiomimetic Single‐Atom Nanozyme for Dual Starvation‐Enhanced Breast Cancer Immunotherapy
Zhang, N., Ping, W., Xiang, J., Chu, S., Li, D., Ning, S., Zhu, D., Zeng, W., & Xu, Q. (2024) · Advanced Healthcare Materials · doi:10.1002/adhm.202401362 · Cited by 42 · see citing works
Self-citationPancreatic Cancer: “A Riddle Wrapped in a Mystery inside an Enigma”
Borazanci, E. H., Dang, C. V., Robey, R. W., Bates, S. E., Chabot, J. A., & Hoff, D. D. V. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-2070 · Cited by 42 · see citing works
“Glutaminase inhibition in combination with metformin, which inhibits mitochondrial function, seems to be synergistic in highly simplified preclinical models (40).”
BackgroundThe Intratumoral Heterogeneity of Cancer Metabolism
Nabi, K., & Le, A. (2018) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-77736-8_10 · Cited by 40 · see citing works
Self-citationZheng, Y., Su, C., Zhao, L., & Shi, Y. (2017) · Journal of Nanobiotechnology · doi:10.1186/s12951-017-0261-x · Cited by 40 · see citing works
Self-citationMetabolic Reprogramming of Cancer by Chemicals that Target Glutaminase Isoenzymes
Matés, J. M., Campos-Sandoval, J. A., Santos-Jiménez, J. D. L., Segura, J. A., Alonso, F. J., & Márquez, J. (2019) · Current Medicinal Chemistry · doi:10.2174/0929867326666190416165004 · Cited by 40 · see citing works
The Role of Dysfunctional Adipose Tissue in Pancreatic Cancer: A Molecular Perspective
Brocco, D., Florio, R., Lellis, L. D., Veschi, S., Grassadonia, A., Tinari, N., & Cama, A. (2020) · Cancers · doi:10.3390/cancers12071849 · Cited by 39 · see citing works
- 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
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 ›
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