The DOI matches its Crossref record; 48 of the 50 references it cites were found in a registry or an index.
Myc-Driven Glycolysis Is a Therapeutic Target in Glioblastoma
Open accessPublished version of a preprint
Abstract
Purpose: Deregulated Myc drives an oncogenic metabolic state, including pseudohypoxic glycolysis, adapted for the constitutive production of biomolecular precursors to feed rapid tumor cell growth. In glioblastoma, Myc facilitates renewal of the tumor-initiating cell reservoir contributing to tumor maintenance. We investigated whether targeting the Myc-driven metabolic state could be a selectively toxic therapeutic strategy for glioblastoma. Experimental Design: The glycolytic dependency of Myc-driven glioblastoma was tested using 13C metabolic flux analysis, glucose-limiting culture assays, and glycolysis inhibitors, including inhibitors of the NAD+ salvage enzyme nicotinamide phosphoribosyl-transferase (NAMPT), in MYC and MYCN shRNA knockdown and lentivirus overexpression systems and in patient-derived glioblastoma tumorspheres with and without MYC/MYCN amplification. The in vivo efficacy of glycolyic inhibition was tested using NAMPT inhibitors in MYCN-amplified patient-derived glioblastoma orthotopic xenograft mouse models. Results: Enforced Myc overexpression increased glucose flux and expression of glycolytic enzymes in glioblastoma cells. Myc and N-Myc knockdown and Myc overexpression systems demonstrated that Myc activity determined sensitivity and resistance to inhibition of glycolysis. Small-molecule inhibitors of glycolysis, particularly NAMPT inhibitors, were selectively toxic to MYC/MYCN–amplified patient-derived glioblastoma tumorspheres. NAMPT inhibitors were potently cytotoxic, inducing apoptosis and significantly extended the survival of mice bearing MYCN-amplified patient-derived glioblastoma orthotopic xenografts. Conclusions: Myc activation in glioblastoma generates a dependency on glycolysis and an addiction to metabolites required for glycolysis. Glycolytic inhibition via NAMPT inhibition represents a novel metabolically targeted therapeutic strategy for MYC or MYCN-amplified glioblastoma and potentially other cancers genetically driven by Myc. Clin Cancer Res; 22(17); 4452–65. ©2016 AACR.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
In the citing paper
“For example, NAMPT inhibitors may be more effective in contexts of MYC-amplified glioblastoma (Tateishi et al., 2016) or when used in combination with other drugs known to deplete NAD+ pools (Bajrami et al., 2012; Chan et al., 2014).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Tateishi et al., 2016
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Comprehensive genomic characterization defines human glioblastoma genes and core pathways
The Cancer Genome Atlas Research Network (2008) · Nature · doi:10.1038/nature07385 · Cited by 7,735
An Integrated Genomic Analysis of Human Glioblastoma Multiforme
Parsons, D. W., Jones, S., Zhang, X., Lin, J. C.-H., Leary, R. J., Angenendt, P., Mankoo, P., Carter, H., Siu, I.-M., Gallia, G. L., et al. (2008) · Science · doi:10.1126/science.1164382 · Cited by 5,857
The Somatic Genomic Landscape of Glioblastoma
Brennan, C. W., Verhaak, R. G. W., McKenna, A., Campos, B., Noushmehr, H., Salama, S. R., Zheng, S., Chakravarty, D., Sanborn, J. Z., Berman, S. H., et al. (2013) · Cell · doi:10.1016/j.cell.2013.09.034 · Cited by 5,016
The landscape of somatic copy-number alteration across human cancers
Beroukhim, R., Mermel, C. H., Porter, D., Wei, G., Raychaudhuri, S., Donovan, J., Barretina, J., Boehm, J. S., Dobson, J., Urashima, M., et al. (2010) · Nature · doi:10.1038/nature08822 · Cited by 4,017
Dang, C. V. (2012) · Cell · doi:10.1016/j.cell.2012.03.003 · Cited by 3,390
Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas
The Cancer Genome Atlas Research Network (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1402121 · Cited by 3,148
BET Bromodomain Inhibition as a Therapeutic Strategy to Target c-Myc
Delmore, J. E., Issa, G. C., Lemieux, M. E., Rahl, P. B., Shi, J., Jacobs, H. M., Kastritis, E., Gilpatrick, T., Paranal, R. M., Qi, J., et al. (2011) · Cell · doi:10.1016/j.cell.2011.08.017 · Cited by 2,888
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
Glioma Groups Based on 1p/19q, IDH , and TERT Promoter Mutations in Tumors
Eckel‐Passow, J. E., Lachance, D. H., Molinaro, A. M., Walsh, K. M., Decker, P. A., Sicotte, H., Pekmezci, M., Rice, T., Kosel, M., Smirnov, I. V., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1407279 · Cited by 1,981
Reflecting on 25 years with MYC
Meyer, N., & Penn, L. Z. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2231 · Cited by 1,575
Targeting MYC dependence in cancer by inhibiting BET bromodomains
Mertz, J. A., Conery, A. R., Bryant, B. M., Sandy, P., Balasubramanian, S., Mele, D. A., Bergeron, L., & Sims, R. J. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1108190108 · Cited by 1,145
Sugimoto, M., Wong, D. T., Hirayama, A., Soga, T., & Tomita, M. (2009) · Metabolomics · doi:10.1007/s11306-009-0178-y · Cited by 1,011
Quantitative Metabolome Analysis Using Capillary Electrophoresis Mass Spectrometry
Soga, T., Ohashi, Y., Ueno, Y., Naraoka, H., Tomita, M., & Nishioka, T. (2003) · Journal of Proteome Research · doi:10.1021/pr034020m · Cited by 981
Glucose Deprivation Contributes to the Development of KRAS Pathway Mutations in Tumor Cells
Yun, J., Rago, C., Cheong, I., Pagliarini, R., Angenendt, P., Rajagopalan, H., Schmidt, K., Willson, J. K. V., Markowitz, S., Zhou, S., et al. (2009) · Science · doi:10.1126/science.1174229 · Cited by 914
Deregulation of Glucose Transporter 1 and Glycolytic Gene Expression by c-Myc
Osthus, R. C., Shim, H., Kim, S., Li, Q., Reddy, R., Mukherjee, M., Xu, Y., Wonsey, D. R., Lee, L. A., & Dang, C. V. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.c000023200 · Cited by 876
Mutational landscape and clonal architecture in grade II and III gliomas
Suzuki, H., Aoki, K., Chiba, K., Sato, Y., Shiozawa, Y., Shiraishi, Y., Shimamura, T., Niida, A., Motomura, K., Ohka, F., et al. (2015) · Nature Genetics · doi:10.1038/ng.3273 · Cited by 831
p53 and Pten control neural and glioma stem/progenitor cell renewal and differentiation
Zheng, H., Ying, H., Yan, H., Kimmelman, A. C., Hiller, D. J., Chen, A.-J., Perry, S. R., Tonon, G., Chu, G. C., Ding, Z., et al. (2008) · Nature · doi:10.1038/nature07443 · Cited by 767
The NAD metabolome — a key determinant of cancer cell biology
Chiarugi, A., Dölle, C., Felici, R., & Ziegler, M. (2012) · Nature reviews. Cancer · doi:10.1038/nrc3340 · Cited by 660
CDK7 Inhibition Suppresses Super-Enhancer-Linked Oncogenic Transcription in MYCN-Driven Cancer
Chipumuro, E., Marco, E., Christensen, C. L., Kwiatkowski, N. P., Zhang, T., Hatheway, C. M., Abraham, B. J., Sharma, B., Yeung, C. M., Altabef, A. B., et al. (2014) · Cell · doi:10.1016/j.cell.2014.10.024 · Cited by 631
Hasmann, M., & Schemainda, I. (2003) · PubMed · Cited by 617
Amino Acid Analysis by Capillary Electrophoresis Electrospray Ionization Mass Spectrometry
Soga, T., & Heiger, D. N. (2000) · Analytical Chemistry · doi:10.1021/ac990976y · Cited by 520
Soga, T., Ueno, Y., Naraoka, H., Ohashi, Y., Tomita, M., & Nishioka, T. (2002) · Analytical Chemistry · doi:10.1021/ac020064n · Cited by 473
Extreme vulnerability of IDH1 mutant cancers to NAD+ depletion
Tateishi, K., Wakimoto, H., Iafrate, A. J., Tanaka, S., Loebel, F., Lelic, N., Wiederschain, D., Bedel, O., Deng, G., Zhang, B., et al. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.11.006 · Cited by 433
Self-citationc-Myc Is Required for Maintenance of Glioma Cancer Stem Cells
Wang, J., Wang, H., Li, Z., Wu, Q., Lathia, J. D., McLendon, R. E., Hjelmeland, A. B., & Rich, J. N. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003769 · Cited by 430
Kim, H., Zheng, S., Amini, S. S., Virk, S. M., Mikkelsen, T., Brat, D. J., Grimsby, J., Sougnez, C., Muller, F., Hu, J., et al. (2015) · Genome Research · doi:10.1101/gr.180612.114 · Cited by 411
Masui, K., Tanaka, K., Akhavan, D., Babic, I., Gini, B., Matsutani, T., Iwanami, A., Liu, F., Villa, G. R., Gu, Y., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.09.013 · Cited by 407
Exploiting oncogene-induced replicative stress for the selective killing of Myc-driven tumors
Murga, M., Campaner, S., Lopez-Contreras, A. J., Toledo, L. I., Soria, R., Montaña, M. F., D'Artista, L., Schleker, T., Guerra, C., Garcia, E., et al. (2011) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2189 · Cited by 381
Wakimoto, H., Kesari, S., Farrell, C. J., Curry, W. T., Zaupa, C., Aghi, M. K., Kuroda, T., Stemmer-Rachamimov, A. O., Shah, K., Liu, T., et al. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-3886 · Cited by 361
Self-citationSpatiotemporal Evolution of the Primary Glioblastoma Genome
Kim, J., Lee, I., Cho, H. J., Park, C., Jung, Y.-S., Kim, Y., Nam, S. H., Kim, B. S., Johnson, M. D., Kong, D., et al. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.07.013 · Cited by 328
Integrated genomic characterization of IDH1-mutant glioma malignant progression
Bai, H., Harmancı, A. S., Erson-Omay, Z., Li, J., Coşkun, S., Simon, M., Krischek, B., Özduman, K., Omay, S. B., Sorensen, E. A., et al. (2015) · Nature Genetics · doi:10.1038/ng.3457 · Cited by 328
A unique glucose-dependent apoptotic pathway induced by c-Myc
Shim, H., Chun, Y. S., Lewis, B. C., & Dang, C. V. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.4.1511 · Cited by 286
Menssen, A., Hydbring, P., Kapelle, K., Vervoorts, J., Diebold, J., Lüscher, B., Larsson, L., & Hermeking, H. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1105304109 · Cited by 275
Maintenance of primary tumor phenotype and genotype in glioblastoma stem cells
Wakimoto, H., Mohapatra, G., Kanai, R., Curry, W. T., Yip, S. S. F., Nitta, M., Patel, A. P., Barnard, Z. R., Stemmer-Rachamimov, A. O., Louis, D. N., et al. (2011) · Neuro-Oncology · doi:10.1093/neuonc/nor195 · Cited by 245
Self-citationWatson, M., Roulston, A., Bélec, L., Billot, X., Marcellus, R., Bédard, D., Bernier, C., Branchaud, S., Chan, H., Dairi, K., et al. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.00112-09 · Cited by 229
Hui, A. B., Lo, K. W., Yin, X.-L., Poon, W. S., & Ng, H. (2001) · Laboratory Investigation · doi:10.1038/labinvest.3780280 · Cited by 212
Myc inhibition is effective against glioma and reveals a role for Myc in proficient mitosis
Annibali, D., Whitfield, J. R., Favuzzi, E., Jauset, T., Serrano, E., Cuartas, I., Redondo-Campos, S., Folch, G., Gonzàlez-Juncà, A., Sodir, N. M., et al. (2014) · Nature Communications · doi:10.1038/ncomms5632 · Cited by 200
Wakimoto, H., Tanaka, S., Curry, W. T., Loebel, F., Zhao, D., Tateishi, K., Chen, J., Klofas, L. K., Lelic, N., Kim, J. C., et al. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-3052 · Cited by 190
Self-citationTan, B., Young, D. A., Lu, Z.-H., Wang, T., Meier, T. I., Shepard, R. L., Roth, K. D. W., Zhai, Y. W., Huss, K., Kuo, M., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.394510 · Cited by 181
Medicinal Chemistry of Nicotinamide Phosphoribosyltransferase (NAMPT) Inhibitors
Galli, U., Travelli, C., Massarotti, A., Fakhfouri, G., Rahimian, R., Tron, G. C., & Genazzani, A. A. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm4001049 · Cited by 157
Hodgson, J., Yeh, R.-F., Ray, A., Wang, N. J., Smirnov, I. V., Yu, M., Hariono, S., Silber, J., Feiler, H. S., Gray, J. W., et al. (2009) · Neuro-Oncology · doi:10.1215/15228517-2008-113 · Cited by 149
Luan, W., Wang, Y., Chen, X., Shi, Y., Wang, J., Zhang, J., Qian, J., Li, R., Tao, T., Wei, W., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.3514 · Cited by 146
CHS 828, a novel pyridyl cyanoguanidine with potent antitumor activity in vitro and in vivo.
Hjarnaa, P. V., Jonsson, E. W., Latini, S., Dhar, S., Larsson, R., Bramm, E., Skov, T., & Binderup, L. (1999) · PubMed · Cited by 115
Therapeutic Targeting of Myc-Reprogrammed Cancer Cell MetabolismPreprint
Dang, C. V. (2011) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2011.76.011296 · Cited by 104
Wosikowski, K., Mattern, K., Schemainda, I., Hasmann, M., Rattel, B., & Löser, R. (2002) · PubMed · Cited by 89
Shames, D. S., Elkins, K., Walter, K., Holcomb, T., Du, P., Mohl, D. A., Xiao, Y., Pham, T., Haverty, P. M., Liederer, B. M., et al. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-1186 · Cited by 85
Tolstikov, V., Nikolayev, A., Dong, S., Zhao, G., & Kuo, M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0114019 · Cited by 84
Myc increases self-renewal in neural progenitor cells through Miz-1
Kerosuo, L., Piltti, K. M., Fox, H., Angers‐Loustau, A., Häyry, V., Eilers, M., Sariola, H. V., & Wartiovaara, K. (2008) · Journal of Cell Science · doi:10.1242/jcs.024802 · Cited by 66
Zhang, L., Liu, L., Qie, L.-L., Ling, K.-N., Xu, L.-H., Wang, F., Fang, S., Lu, Y., Hu, H., Wei, E.-Q., et al. (2011) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2011.11.017 · Cited by 39
Research works printed but not linked: 1
- Hjarnaa, 1999, CHS 828, a novel pyridyl cyanoguanidine with potent antitumor activity invitro and invivo, Cancer Res, 59, 5751
Cited by
Sorted by citations
Targeting Metabolism for Cancer Therapy
Luengo, A., Gui, D. Y., & Vander Heiden, M. G. (2017) · Cell Chemical Biology · doi:10.1016/j.chembiol.2017.08.028 · Cited by 971
The role of m6A RNA methylation in cancer metabolism
An, Y., & Duan, H. (2022) · Molecular Cancer · doi:10.1186/s12943-022-01500-4 · Cited by 904
NAD+ metabolism, stemness, the immune response, and cancer
Navas, L. E., & Carnero, A. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00354-w · Cited by 551
LncRNA LINRIS stabilizes IGF2BP2 and promotes the aerobic glycolysis in colorectal cancer
Wang, Y., Lu, J.-H., Wu, Q.-N., Jin, Y., Wang, D.-S., Chen, Y.-X., Liu, J., Luo, X.-J., Meng, Q., Pu, H.-Y., et al. (2019) · Molecular Cancer · doi:10.1186/s12943-019-1105-0 · Cited by 507
Tumors exploit FTO-mediated regulation of glycolytic metabolism to evade immune surveillance
Liu, Y., Liang, G., Xu, H., Dong, W., Dong, Z., Qiu, Z., Zhang, Z., Li, F., Huang, Y., Li, Y., et al. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.04.001 · Cited by 374
Metadata
- Authors
- Tateishi, K., Iafrate, A. J., Ho, Q., Curry, W. T., Batchelor, T. T., Flaherty, K. T., Onozato, M. L., Lelic, N., Sundaram, S., Cahill, D. P., Chi, A. S., & Wakimoto, H.
- Affiliations
- Harvard University (US)
- NYU Langone Health (US)
- Corresponding author
- Cahill, Daniel P.
- Chi, Andrew S.
- Wakimoto, Hiroaki
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2016-08-31
- Volume
- 22
- Issue
- 17
- Pages
- 4452-4465
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- PMC
- PMC5010492
- OpenAlex
- W2341529963
- Cited by
- 160
- References
- 50
- Citations by year
- 2026: 11 · 2025: 15 · 2024: 11 · 2023: 21 · 2022: 22 · 2021: 28 · 2020: 21 · 2019: 15 · 2018: 3 · 2017: 10 · 2016: 3
- FWCI
- 4.31
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Japan Society for the Promotion of Science (16K10765)
- National Cancer Institute (K24CA125440, P50CA165962)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Oncology › Glioma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- glioblastoma, c-Myc, MYCN amplification, glycolysis, NAMPT inhibitors, cancer metabolism, metabolic targeting therapy, cancer stem cells, glucose flux, apoptosis, orthotopic xenograft
- MeSH terms
- Animals, Antineoplastic Agents, Disease Models, Animal, Gene Amplification, Glioblastoma, Glucose, Glycolysis, Humans, NAD, Proto-Oncogene Proteins c-myc, Apoptosis, Xenograft Model Antitumor Assays, RNA Interference, RNA, Small Interfering, Cell Line, Tumor, Mice, Nicotinamide Phosphoribosyltransferase
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
