{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T11:43:34Z","timestamp":1792669414419,"version":"4.5.0"},"reference-count":125,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,12,29]],"date-time":"2019-12-29T00:00:00Z","timestamp":1577577600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The ability of 2-deoxy-d-glucose (2-DG) to interfere with d-glucose metabolism demonstrates that nutrient and energy deprivation is an efficient tool to suppress cancer cell growth and survival. Acting as a d-glucose mimic, 2-DG inhibits glycolysis due to formation and intracellular accumulation of 2-deoxy-d-glucose-6-phosphate (2-DG6P), inhibiting the function of hexokinase and glucose-6-phosphate isomerase, and inducing cell death. In addition to glycolysis inhibition, other molecular processes are also affected by 2-DG. Attempts to improve 2-DG\u2019s drug-like properties, its role as a potential adjuvant for other chemotherapeutics, and novel 2-DG analogs as promising new anticancer agents are discussed in this review.<\/jats:p>","DOI":"10.3390\/ijms21010234","type":"journal-article","created":{"date-parts":[[2019,12,30]],"date-time":"2019-12-30T05:49:41Z","timestamp":1577684981000},"page":"234","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":563,"title":["2-Deoxy-d-Glucose and Its Analogs: From Diagnostic to Therapeutic Agents"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3565-8860","authenticated-orcid":false,"given":"B.","family":"Pajak","sequence":"first","affiliation":[{"name":"Independent Laboratory of Genetic and Molecular Biology, Kaczkowski Military Institute of Hygiene and Epidemiology, Kozielska 4, 01-163 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Siwiak","sequence":"additional","affiliation":[{"name":"Independent Laboratory of Genetic and Molecular Biology, Kaczkowski Military Institute of Hygiene and Epidemiology, Kozielska 4, 01-163 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"So\u0142tyka","sequence":"additional","affiliation":[{"name":"Independent Laboratory of Genetic and Molecular Biology, Kaczkowski Military Institute of Hygiene and Epidemiology, Kozielska 4, 01-163 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Priebe","sequence":"additional","affiliation":[{"name":"Texas Oncology, Division of Gynecologic Oncology, 910 E. Houston Street, Tyler, TX 75702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Zieli\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, 1901 East Rd., Houston, TX 77054, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Fokt","sequence":"additional","affiliation":[{"name":"Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, 1901 East Rd., Houston, TX 77054, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Ziemniak","sequence":"additional","affiliation":[{"name":"Biological and Chemical Research Centre, Department of Chemistry, University of Warsaw, 02-089 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1454-0852","authenticated-orcid":false,"given":"A.","family":"Ja\u015bkiewicz","sequence":"additional","affiliation":[{"name":"Independent Laboratory of Genetic and Molecular Biology, Kaczkowski Military Institute of Hygiene and Epidemiology, Kozielska 4, 01-163 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Borowski","sequence":"additional","affiliation":[{"name":"Independent Laboratory of Genetic and Molecular Biology, Kaczkowski Military Institute of Hygiene and Epidemiology, Kozielska 4, 01-163 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Domoradzki","sequence":"additional","affiliation":[{"name":"Independent Laboratory of Genetic and Molecular Biology, Kaczkowski Military Institute of Hygiene and Epidemiology, Kozielska 4, 01-163 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.","family":"Priebe","sequence":"additional","affiliation":[{"name":"Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, 1901 East Rd., Houston, TX 77054, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0092-8674(00)81683-9","article-title":"The hallmarks of cancer","volume":"100","author":"Hanahan","year":"2000","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: The next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1007\/BF01712130","article-title":"Versuche an uberlebendem carcinomgewebe","volume":"2","author":"Warburg","year":"1923","journal-title":"Klin. Wochenschr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"83","DOI":"10.2147\/HP.S93413","article-title":"The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy","volume":"3","author":"Muz","year":"2015","journal-title":"Hypoxia"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/s002680020338","article-title":"Overview of glucose regulation","volume":"25","author":"Tirone","year":"2001","journal-title":"World J. Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1079\/BJN2002763","article-title":"Glucose transporters (GLUT and SGLT): Expanded families of sugar transport proteins","volume":"89","author":"Wood","year":"2003","journal-title":"Br. J. Nutr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2436","DOI":"10.1111\/j.1742-4658.2011.08174.x","article-title":"Enzymatic features of the glucose metabolism in tumor cells","volume":"278","author":"Herling","year":"2011","journal-title":"FEBS J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.pharmthera.2008.09.005","article-title":"Nutrient transporters in cancer: Relevance to Warburg hypothesis and beyond","volume":"121","author":"Ganapathy","year":"2009","journal-title":"Pharmacol. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"7023","DOI":"10.1113\/JP273839","article-title":"Oxidative phosphorylation: Regulation and role in cellular and tissue metabolism","volume":"595","author":"Wilson","year":"2017","journal-title":"J. Physiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1126\/science.1160809","article-title":"Understanding the Warburg effect: The metabolic requirements of cell proliferation","volume":"324","author":"Cantley","year":"2009","journal-title":"Science"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.bbabio.2010.10.012","article-title":"Choosing between glycolysis and oxidative phosphorylation: A tumor\u2019s dilemma?","volume":"1807","author":"Jose","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1038\/nrc1478","article-title":"Why do cancers have high aerobic glycolysis?","volume":"4","author":"Gatenby","year":"2004","journal-title":"Nat. Rev. Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"16767","DOI":"10.1074\/jbc.M901790200","article-title":"Genome-wide Association of Hypoxia-inducible Factor (HIF)-1\u03b1 and HIF-2\u03b1 DNA Binding with Expression Profiling of Hypoxia-inducible Transcripts","volume":"284","author":"Mole","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1101\/gad.12.2.149","article-title":"Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1 alpha","volume":"12","author":"Iyer","year":"1998","journal-title":"Genes Dev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"10892","DOI":"10.1074\/jbc.M800102200","article-title":"Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxia","volume":"283","author":"Zhang","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.cell.2007.01.047","article-title":"HIF-1 regulates cytochrome oxidase subunits to optimize efficiency of respiration in hypoxic cells","volume":"129","author":"Fukuda","year":"2007","journal-title":"Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.gde.2009.10.009","article-title":"HIF-1: Upstream and downstream of cancer metabolism","volume":"20","author":"Semenza","year":"2010","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/j.ccr.2008.05.005","article-title":"Tumor Cell Metabolism: Cancer\u2019s Achilles\u2019 Heel","volume":"13","author":"Kroemer","year":"2008","journal-title":"Cancer Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1084\/jem.20120162","article-title":"Targeting glucose metabolism for cancer therapy","volume":"209","author":"Hamanaka","year":"2012","journal-title":"J. Exp. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1038\/nature06734","article-title":"The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth","volume":"452","author":"Christofk","year":"2008","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.semcdb.2015.08.004","article-title":"Pyruvate kinase: Function, regulation and role in cancer","volume":"43","author":"Israelsen","year":"2015","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/j.biocel.2010.02.005","article-title":"Pyruvate kinase type M2: A key regulator of the metabolic budget system in tumor cells","volume":"43","author":"Mazurek","year":"2011","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.canlet.2014.09.003","article-title":"2-Deoxy-d-glucose targeting of glucose metabolism in cancer cells as a potential therapy","volume":"355","author":"Zhang","year":"2014","journal-title":"Cancer Lett."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"13464","DOI":"10.18632\/oncotarget.7229","article-title":"Targeting hypoxic response for cancer therapy","volume":"7","author":"Paolicchi","year":"2016","journal-title":"Oncotarget"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e1065","DOI":"10.1038\/cddis.2014.38","article-title":"Metabolism addiction in pancreatic cancer","volume":"5","author":"Blum","year":"2014","journal-title":"Cell Death Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"43","DOI":"10.3389\/fcell.2017.00043","article-title":"Metabolic Reprogramming in Glioma","volume":"5","author":"Strickland","year":"2017","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_27","first-page":"460","article-title":"Cancer metabolism as a therapeutic target","volume":"27","author":"Batra","year":"2013","journal-title":"Oncology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"771","DOI":"10.2174\/1871520614666140416105309","article-title":"3-Bromopyruvic acid, a hexokinase II inhibitor, is an effective antitumor agent on hepatoma cells: In vitro and in vivo findings","volume":"14","author":"Gong","year":"2014","journal-title":"Anticancer Agents Med. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"260146","DOI":"10.1155\/2008\/260146","article-title":"Arsenic-based antineoplastic drugs and their mechanisms of action","volume":"2008","author":"Ralph","year":"2008","journal-title":"Met. Based Drugs"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/j.bbabio.2009.03.003","article-title":"Role of mitochondria-associated hexokinase II in cancer cell death induced by 3-bromopyruvate","volume":"1787","author":"Chen","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1038\/sj.bjc.6600547","article-title":"Evaluation of 2-deoxy-d-glucose as a chemotherapeutic agent: Mechanism of cell death","volume":"87","author":"Aft","year":"2002","journal-title":"Br. J. Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1007\/s00280-003-0724-7","article-title":"Greater cell cycle inhibition and cytotoxicity induced by 2-deoxy-d-glucose in tumor cells treated under hypoxic vs. aerobic conditions","volume":"53","author":"Maher","year":"2004","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Kunjithapatham, R., Geschwind, J.-F.H., Rao, P.P., Boronina, T.N., Cole, R.N., and Ganapathy-Kanniappan, S. (2013). Systemic administration of 3-bromopyruvate reveals its interaction with serum proteins in a rat model. BMC Res. Notes, 6.","DOI":"10.1186\/1756-0500-6-277"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s12551-015-0186-2","article-title":"Glucose transporters: Physiological and pathological roles","volume":"8","author":"Navale","year":"2016","journal-title":"Biophys. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1002\/cphy.c110024","article-title":"Role of monosaccharide transport proteins in carbohydrate assimilation, distribution, metabolism, and homeostasis","volume":"2","author":"Cura","year":"2012","journal-title":"Compr. Physiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.neuroimage.2016.08.040","article-title":"Glucose metabolism-weighted imaging with chemical exchange-sensitive MRI of 2-deoxyglucose (2DG) in brain: Sensitivity and biological sources","volume":"143","author":"Jin","year":"2016","journal-title":"Neuroimage"},{"key":"ref_37","first-page":"49","article-title":"Pharmacologic Activation of Tumor Hypoxia: A Means to Increase Tumor 2-Deoxy-2-[F-18]Fluoro-d-Glucose Uptake?","volume":"12","author":"Mees","year":"2013","journal-title":"Mol. Imaging"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Zhou, H., Luby-Phelps, K., Mickey, B.E., Habib, A.A., Mason, R.P., and Zhao, D. (2009). Dynamic near-infrared optical imaging of 2-deoxyglucose uptake by intracranial glioma of athymic mice. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0008051"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1111\/j.1471-4159.1977.tb03919.x","article-title":"Relation between physiological function and energy metabolism in the central nervous system","volume":"29","author":"Sokoloff","year":"1977","journal-title":"J. Neurochem."},{"key":"ref_40","first-page":"394","article-title":"Fluorine-18-fluorodeoxyglucose PET to determine regional cerebral glucose utilization: A re-examination","volume":"37","author":"Schmidt","year":"1996","journal-title":"J. Nucl. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1002\/iub.1251","article-title":"The wonders of 2-deoxy-d-glucose","volume":"66","author":"Xi","year":"2014","journal-title":"IUBMB J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1002\/ijc.31299","article-title":"In vivo characterization of brain metabolism by 1H MRS, 13C MRS and 18FDG PET reveals significant glucose oxidation of invasively growing glioma cells","volume":"143","author":"Lai","year":"2018","journal-title":"Int. J. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.cpet.2017.11.004","article-title":"[18F]-2-Fluoro-2-Deoxy-d-glucose-PET Assessment of Cervical Cancer","volume":"13","author":"Viswanathan","year":"2018","journal-title":"PET Clin."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3442","DOI":"10.12659\/MSM.895034","article-title":"2-DG-regulated RIP and cFLIP effect on liver cancer cells apoptosis induced by TRAIL","volume":"10","author":"Zhang","year":"2015","journal-title":"Med. Sci. Monit."},{"key":"ref_45","first-page":"70","article-title":"The role of glucose transporters in human metabolic regulation","volume":"59","author":"Magier","year":"2013","journal-title":"Postepy Biochem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e188","DOI":"10.1038\/oncsis.2015.46","article-title":"Energy disruptors: Rising stars in anticancer therapy?","volume":"5","author":"Bost","year":"2016","journal-title":"Oncogenesis"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1007\/s00280-010-1391-0","article-title":"2-Deoxy-d-glucose activates autophagy via endoplasmic reticulum stress rather than ATP depletion","volume":"67","author":"Xi","year":"2011","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.12688\/f1000research.11960.1","article-title":"AMP-activated protein kinase\u2014Not just an energy sensor","volume":"6","author":"Hardie","year":"2017","journal-title":"F1000 Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1016\/j.febslet.2010.01.017","article-title":"mTOR regulation of autophagy","volume":"584","author":"Jung","year":"2010","journal-title":"FEBS Lett."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Levine, B., Yoshimori, T., and Deretic, V. (2009). Physiological Functions of Autophagy. Autophagy in Infection and Immunity, Springer. Current Topics in Microbiology and Immunology.","DOI":"10.1007\/978-3-642-00302-8"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/cr.2013.168","article-title":"The machinery of macroautophagy","volume":"24","author":"Feng","year":"2014","journal-title":"Cell Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1007\/s12272-015-0562-2","article-title":"Integrating autophagy and metabolism in cancer","volume":"38","author":"Cheong","year":"2015","journal-title":"Arch. Pharm. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1158\/1535-7163.MCT-11-0047","article-title":"The role of autophagy in cancer: Therapeutic implications","volume":"10","author":"Yang","year":"2011","journal-title":"Mol. Cancer Ther."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"8204","DOI":"10.1073\/pnas.0502857102","article-title":"The coordinate regulation of the p53 and mTOR pathways in cells","volume":"102","author":"Feng","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"285","DOI":"10.3389\/fonc.2014.00285","article-title":"p53 Family and Cellular Stress Responses in Cancer","volume":"4","author":"Pflaum","year":"2014","journal-title":"Front. Oncol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1002\/jcp.25129","article-title":"Autophagy-Induced Apoptosis in Lung Cancer Cells by a Novel Digitoxin Analog","volume":"231","author":"Kulkarni","year":"2016","journal-title":"J. Cell. Physiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1080\/15548627.2015.1091141","article-title":"ER stress: Autophagy induction, inhibition and selection","volume":"11","author":"Rashid","year":"2015","journal-title":"Autophagy"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"853","DOI":"10.4161\/cbt.9.11.11632","article-title":"2-deoxy-d-glucose induces oxidative stress and cell killing in human neuroblastoma cells","volume":"9","author":"Shutt","year":"2010","journal-title":"Cancer. Biol. Ther."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"66","DOI":"10.4161\/auto.1.2.1738","article-title":"Does autophagy contribute to cell death?","volume":"1","author":"Debnath","year":"2005","journal-title":"Autophagy"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"12759","DOI":"10.1074\/jbc.M212392200","article-title":"Inhibition of Glucose Metabolism Sensitizes Tumor Cells to Death Receptor-triggered Apoptosis through Enhancement of Death-inducing Signaling Complex Formation and Apical Procaspase-8 Processing","volume":"278","author":"Palacios","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1158\/0008-5472.613.65.2","article-title":"Inhibition of glycolysis in cancer cells: A novel strategy to overcome drug resistance associated with mitochondrial respiratory defect and hypoxia","volume":"65","author":"Xu","year":"2005","journal-title":"Cancer Res."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Wang, Q., Liang, B., Shirwany, N.A., and Zou, M.-H. (2011). 2-Deoxy-d-glucose treatment of endothelial cells induces autophagy by reactive oxygen species-mediated activation of the AMP-activated protein kinase. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0017234"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.4161\/cbt.8.13.8869","article-title":"Combining 2-deoxy-d-glucose with electron transport chain blockers","volume":"8","author":"Boutros","year":"2009","journal-title":"Cancer Biol. Ther."},{"key":"ref_64","first-page":"511","article-title":"Is targeting glycolysis with 2-deoxyglucose a viable therapeutic approach to bladder cancer?","volume":"5","author":"Valera","year":"2017","journal-title":"Int. J. Cnacer Ther. Oncol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Kim, P.-J., Lee, D.-Y., and Jeong, H. (2009). Centralized Modularity of N-Linked Glycosylation Pathways in Mammalian Cells. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0007317"},{"key":"ref_66","unstructured":"Stanley, P., Schachter, H., and Taniguchi, N. (2009). Chapter 8. N-Glycans. Essentials of Glycobiology, Cold Spring Harbor Laboratory Press. [2nd ed.]."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/978-1-4939-1154-7_3","article-title":"Synthesis, processing, and function of N-glycans in N-glycoproteins","volume":"9","author":"Biberich","year":"2014","journal-title":"Adv. Neurobiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3049","DOI":"10.1158\/1535-7163.MCT-07-0310","article-title":"Under normoxia, 2-deoxy-d-glucose elicits cell death in select tumor types not by inhibition of glycolysis but by interfering with N-linked glycosylation","volume":"6","author":"Kurtoglu","year":"2007","journal-title":"Mol. Cancer Ther."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1007\/s10549-018-4874-z","article-title":"Protein N-glycosylation alteration and glycolysis inhibition both contribute to the antiproliferative action of 2-deoxyglucose in breast cancer cells","volume":"171","author":"Berthe","year":"2018","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_70","first-page":"CB-03","article-title":"2-Deoxy-d-glucose inhibits N-glycosylation in glioblastoma multiforme-derived cancer stem cells","volume":"12","author":"Emmett","year":"2010","journal-title":"Neuro-Oncol."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Priebe, W., Emmett, M.R., Ji, J., Fokt, I., Skora, S., Conrad, C., Wang, X., and Marshall, A.G. (2011). 2-DG inhibits of N-glycosylation in glioblstaoma-derived cancer stem cells. Cancer Res.","DOI":"10.1158\/1538-7445.AM2011-2304"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.4161\/cbt.5.9.2986","article-title":"Differential mechanisms of radiosensitization by 2-deoxy-d-glucose in the monolayers and multicellular spheroids of a human glioma cell line","volume":"5","author":"Khaitan","year":"2006","journal-title":"Cancer Biol. Ther."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"188","DOI":"10.3892\/br.2013.211","article-title":"High glucose-induced resistance to 5-fluorouracil in pancreatic cancer cells alleviated by 2-deoxy-d-glucose","volume":"2","author":"Cheng","year":"2014","journal-title":"Biomed. Rep."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1158\/1535-7163.MCT-06-0407","article-title":"Hypoxia-inducible factor-1 confers resistance to the glycolytic inhibitor 2-deoxy-d-glucose","volume":"6","author":"Maher","year":"2007","journal-title":"Mol. Cancer Ther."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"3251","DOI":"10.1158\/1538-7445.AM2013-3251","article-title":"Blockade of HIF-1 with a small molecule inhibitor WP1066 in melanoma","volume":"73","author":"Jayakumar","year":"2013","journal-title":"Cancer Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1002\/pros.21172","article-title":"Targeting tumor metabolism with 2-deoxyglucose in patients with castrate-resistant prostate cancer and advanced malignancies","volume":"70","author":"Stein","year":"2010","journal-title":"Prostate"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1007\/s00280-012-2045-1","article-title":"A phase I dose-escalation trial of 2-deoxy-d-glucose alone or combined with docetaxel in patients with advanced solid tumors","volume":"71","author":"Raez","year":"2013","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_78","first-page":"3413","article-title":"2-Deoxy-d-glucose-induced cytotoxicity and radiosensitization in tumor cells is mediated via disruptions in thiol metabolism","volume":"63","author":"Lin","year":"2003","journal-title":"Cancer Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1038\/nrc3958","article-title":"The tumour microenvironment after radiotherapy: Mechanisms of resistance and recurrence","volume":"15","author":"Barker","year":"2015","journal-title":"Nat. Rev. Cancer."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1080\/09553008614550981","article-title":"The Oxygen Effect in Radiation Inactivation of DNA and Enzymes","volume":"50","author":"Quintiliani","year":"1986","journal-title":"Int. J. Radiat. Biol. Relat. Stud. Phys. Chem. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"463","DOI":"10.2307\/3575919","article-title":"Energetics of Cellular Repair Processes in a Respiratory-Deficient Mutant of Yeast","volume":"92","author":"Jain","year":"1982","journal-title":"Radiat. Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1016\/S0360-3016(01)01534-6","article-title":"Heterogeneity in 2-deoxy-d-glucose-induced modifications in energetics and radiation responses of human tumor cell lines","volume":"50","author":"Dwarkanath","year":"2001","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1903","DOI":"10.1158\/1078-0432.CCR-06-2094","article-title":"Combining radioimmunotherapy with antihypoxia therapy 2-deoxy-d-glucose results in reduction of therapeutic efficacy","volume":"13","author":"Dearling","year":"2007","journal-title":"Clin. Cancer Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1007\/s00066-005-1320-z","article-title":"Optimizing cancer radiotherapy with 2-deoxy-d-glucose dose escalation studies in patients with glioblastoma multiforme","volume":"181","author":"Singh","year":"2005","journal-title":"Strahlenther. Onkol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"30","DOI":"10.18689\/mjo-1000105","article-title":"Radiosensitization of prostate cancer cells by 2-deoxy-d-glucose","volume":"2","author":"Rae","year":"2018","journal-title":"Madridge J. Oncogen."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"12347","DOI":"10.1007\/s13277-016-5089-8","article-title":"Synergistic increase in efficacy of a combination of 2-deoxy-d-glucose and cisplatin in normoxia and hypoxia: Switch from autophagy to apoptosis","volume":"37","author":"Jalota","year":"2016","journal-title":"Tumour Biol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"3364","DOI":"10.1158\/0008-5472.CAN-06-3717","article-title":"2-Deoxy-d-glucose combined with cisplatin enhances cytotoxicity via metabolic oxidative stress in human head and neck cancer cells","volume":"67","author":"Simons","year":"2007","journal-title":"Cancer Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1038\/s41598-017-01801-5","article-title":"Combined treatment with Metformin and 2-deoxy glucose induces detachment of viable MDA-MB-231 breast cancer cells in vitro","volume":"7","author":"Bizjak","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1182\/blood.V122.21.1665.1665","article-title":"The Combination Of 2-DG and Metformin Inhibits The mTORC1 Pathway and Suppresses Aggressive B Cell Lymphoma Growth and Survival","volume":"122","author":"Bi","year":"2013","journal-title":"Blood"},{"key":"ref_90","first-page":"4812","article-title":"Targeting cancer cell metabolism: The combination of metformin and 2-Deoxyglucose regulates apoptosis in ovarian cancer cells via p38 MAPK\/JNK signaling pathway","volume":"8","author":"Zhu","year":"2016","journal-title":"Am. J. Transl. Res."},{"key":"ref_91","first-page":"197","article-title":"Inhibition of glioblastoma tumorspheres by combined treatment with 2-deoxyglucose and metformin","volume":"19","author":"Kim","year":"2017","journal-title":"Neuro-Oncol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.ijpharm.2017.08.095","article-title":"Targeting energy metabolism of cancer cells: Combined administration of NCL-240 and 2-DG","volume":"532","author":"Pattni","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Wang, S.-Y., Wei, Y.-H., Shieh, D.-B., Lin, L.-L., Cheng, S.-P., Wang, P.-W., and Chuang, J.-H. (2015). 2-Deoxy-d-Glucose Can Complement Doxorubicin and Sorafenib to Suppress the Growth of Papillary Thyroid Carcinoma Cells. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0130959"},{"key":"ref_94","first-page":"739","article-title":"2DG enhances the susceptibility of breast cancer cells to doxorubicin","volume":"5","author":"Ahmad","year":"2010","journal-title":"Cent. Eur. J. Biol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"3213","DOI":"10.7314\/APJCP.2015.16.8.3213","article-title":"2-deoxy-d-Glucose Synergizes with Doxorubicin or l-Buthionine Sulfoximine to Reduce Adhesion and Migration of Breast Cancer Cells","volume":"16","author":"Mustafa","year":"2015","journal-title":"Asian Pac. J. Cancer Prev. APJCP"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1007\/s00280-006-0291-9","article-title":"Glucose uptake inhibitor sensitizes cancer cells to daunorubicin and overcomes drug resistance in hypoxia","volume":"59","author":"Cao","year":"2007","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"129","DOI":"10.3727\/105221616X693855","article-title":"Sorafenib and 2-Deoxyglucose Synergistically Inhibit Proliferation of both Sorafenib Sensitive and Resistant HCC Cells by Inhibiting ATP Production","volume":"17","author":"Reyes","year":"2017","journal-title":"Gene Expr."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"800","DOI":"10.3892\/ol.2016.5510","article-title":"2-Deoxyglucose and sorafenib synergistically suppress the proliferation and motility of hepatocellular carcinoma cells","volume":"13","author":"Tomizawa","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1158\/0008-5472.CAN-03-3294","article-title":"2-deoxy-d-glucose increases the efficacy of adriamycin and paclitaxel in human osteosarcoma and non-small cell lung cancers in vivo","volume":"64","author":"Maschek","year":"2004","journal-title":"Cancer Res."},{"key":"ref_100","first-page":"6623","article-title":"2-Deoxy-d-glucose Sensitizes Cancer Cells to Barasertib and Everolimus by ROS-independent Mechanism(s)","volume":"35","author":"Zhelev","year":"2015","journal-title":"Anticancer Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"e284","DOI":"10.1038\/cddis.2012.24","article-title":"FTS and 2-DG induce pancreatic cancer cell death and tumor shrinkage in mice","volume":"3","author":"Goldberg","year":"2012","journal-title":"Cell Death Dis."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"5175","DOI":"10.1016\/j.bbagen.2013.07.010","article-title":"Berberine combined with 2-deoxy-d-glucose synergistically enhances cancer cell proliferation inhibition via energy depletion and unfolded protein response disruption","volume":"1830","author":"Fan","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"36461","DOI":"10.18632\/oncotarget.9263","article-title":"Combining 2-deoxy-d-glucose with fenofibrate leads to tumor cell death mediated by simultaneous induction of energy and ER stress","volume":"7","author":"Liu","year":"2016","journal-title":"Oncotarget"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.apsb.2015.06.002","article-title":"Regulation of AMP-activated protein kinase by natural and synthetic activators","volume":"6","author":"Hardie","year":"2016","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2634","DOI":"10.1158\/0008-5472.CAN-11-3928","article-title":"Mitochondria-targeted drugs synergize with 2-deoxyglucose to trigger breast cancer cell death","volume":"72","author":"Cheng","year":"2012","journal-title":"Cancer Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.3109\/10428194.2014.963575","article-title":"Glycolytic inhibitor 2-deoxy-d-glucose suppresses cell proliferation and enhances methylprednisolone sensitivity in non-Hodgkin lymphoma cells through down-regulation of HIF-1\u03b1 and c-MYC","volume":"56","author":"Pang","year":"2015","journal-title":"Leuk. Lymphoma"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"5701","DOI":"10.2147\/IJN.S135849","article-title":"Co-delivery nanocarriers targeting folate receptor and encapsulating 2-deoxyglucose and \u03b1-tocopheryl succinate enhance anti-tumor effect in vivo","volume":"12","author":"Lei","year":"2017","journal-title":"Int. J. Nanomed."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1158\/1535-7163.MCT-12-1188","article-title":"Glycolysis inhibition sensitizes non-small cell lung cancer with T790M mutation to irreversible EGFR inhibitors via translational suppression of Mcl-1 by AMPK activation","volume":"12","author":"Kim","year":"2013","journal-title":"Mol. Cancer Ther."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"87","DOI":"10.4161\/cbt.4.1.1381","article-title":"The glycolytic inhibitor 2-deoxy-d-glucose enhances the efficacy of etoposide in ehrlich ascites tumor-bearing mice","volume":"4","author":"Gupta","year":"2005","journal-title":"Cancer Biol. Ther."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Gao, C., Shen, Y., Jin, F., Miao, Y., and Qiu, X. (2016). Cancer Stem Cells in Small Cell Lung Cancer Cell Line H446: Higher Dependency on Oxidative Phosphorylation and Mitochondrial Substrate-Level Phosphorylation than Non-Stem Cancer Cells. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0154576"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.canlet.2013.03.020","article-title":"Differential sensitivities of glioblastoma cell lines towards metabolic and signaling pathway inhibitions","volume":"336","author":"Kennedy","year":"2013","journal-title":"Cancer Lett."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"103657","DOI":"10.18632\/oncotarget.21761","article-title":"Metabolic alterations underlying Bevacizumab therapy in glioblastoma cells","volume":"8","author":"Valbom","year":"2017","journal-title":"Oncotarget"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"4585","DOI":"10.1158\/0008-5472.CAN-11-0127","article-title":"Overcoming Trastuzumab Resistance in Breast Cancer by Targeting Dysregulated Glucose Metabolism","volume":"71","author":"Zhao","year":"2011","journal-title":"Cancer Res."},{"key":"ref_114","first-page":"743","article-title":"2-deoxy-d-glucose combined with ferulic acid enhances radiation response in non-small cell lung carcinoma cells","volume":"6","author":"Reddy","year":"2011","journal-title":"Cent. Eur. J. Biol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"90","DOI":"10.3389\/fmolb.2019.00090","article-title":"2-deoxyglucose and Newcastle Disease virus synergize to kill breast cancer cells by inhibition of glycolysis pathway through glyceraldehyde3-phosphate downregulation","volume":"6","author":"Abdullah","year":"2019","journal-title":"Front. Mol. Biosci."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.redox.2014.12.001","article-title":"Combined inhibition of glycolysis, the pentose cycle, and thioredoxin metabolism selectively increases cytotoxicity and oxidative stress in human breast and prostate cancer","volume":"4","author":"Li","year":"2015","journal-title":"Redox Biol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1203\/00006450-198404000-00011","article-title":"The 2-deoxyglucose test as a supplement to fasting for detection of childhood hypoglycemia","volume":"18","author":"Hansen","year":"1984","journal-title":"Pediatri. Res."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"336","DOI":"10.3109\/07853890.2013.785233","article-title":"Comparison of normal fsting and one-hour glucose levels as predictors of future diabetes during a 34-year follow-up","volume":"45","author":"Strandberg","year":"2013","journal-title":"Ann. Med."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1007\/s00280-006-0207-8","article-title":"Efficacy of 2-halogen substituted d-glucose analogs in blocking glycolysis and killing \u201chypoxic tumor cells\u201d","volume":"58","author":"Lampidis","year":"2006","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1097\/00008390-200202000-00006","article-title":"Variability in glucose transporter-1 levels and hexokinase activity in human melanoma","volume":"12","author":"Wachsberger","year":"2002","journal-title":"Melanoma Res."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1038\/nrc1367","article-title":"Exploiting tumour hypoxia in cancer treatment","volume":"4","author":"Brown","year":"2004","journal-title":"Nat. Rev. Cancer."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1111\/j.1432-1033.1978.tb12630.x","article-title":"Formation of 2-deoxyglucose-containing lipid-linked oligosaccharides. Interference with glycosylation of glycoproteins","volume":"90","author":"Datema","year":"1978","journal-title":"Eur. J. Biochem."},{"key":"ref_123","first-page":"3359","article-title":"2-Deoxy-2-fluoro-d-mannose induces type II cell death in gliomas","volume":"68","author":"Antanovic","year":"2008","journal-title":"Cancer Res."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"vi86","DOI":"10.1093\/neuonc\/noy148.356","article-title":"EXTH-07. Design and evaluation of WP1122, in inhibitor of glycolysis with increased CNS uptake","volume":"20","author":"Priebe","year":"2018","journal-title":"Neuro-Oncology"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1148\/radiol.2019182919","article-title":"Hyperpolarized pyruvate MR spectroscopy depicts glycolytic inhibition in a mouse model of glioma","volume":"293","author":"Keith","year":"2019","journal-title":"Radiology"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/1\/234\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:46:31Z","timestamp":1760190391000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/1\/234"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,29]]},"references-count":125,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,1]]}},"alternative-id":["ijms21010234"],"URL":"https:\/\/doi.org\/10.3390\/ijms21010234","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,29]]}}}