{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:46:16Z","timestamp":1790729176989,"version":"4.1.0"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T00:00:00Z","timestamp":1624233600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T00:00:00Z","timestamp":1624233600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/501100000833","name":"Rosetrees Trust","doi-asserted-by":"publisher","award":["CM209"],"award-info":[{"award-number":["CM209"]}],"id":[{"id":"10.13039\/501100000833","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurooncol"],"published-print":{"date-parts":[[2021,7]]},"DOI":"10.1007\/s11060-021-03786-8","type":"journal-article","created":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T05:02:46Z","timestamp":1624251766000},"page":"487-496","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["A Phase I clinical trial of dose-escalated metabolic therapy combined with concomitant radiation therapy in high-grade glioma"],"prefix":"10.1007","volume":"153","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0734-7536","authenticated-orcid":false,"given":"Keren","family":"Porper","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yael","family":"Shpatz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luba","family":"Plotkin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronit Goldman","family":"Pechthold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alisa","family":"Talianski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin E.","family":"Champ","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orit","family":"Furman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariel","family":"Shimoni-Sebag","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zvi","family":"Symon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uri","family":"Amit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rina","family":"Hemi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Kanety","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yael","family":"Mardor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zvi R.","family":"Cohen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisheva","family":"Jan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hili","family":"Genssin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yair","family":"Anikster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leor","family":"Zach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9959-2485","authenticated-orcid":false,"given":"Yaacov R.","family":"Lawrence","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,21]]},"reference":[{"key":"3786_CR1","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1056\/NEJMoa043330","volume":"352","author":"R Stupp","year":"2005","unstructured":"Stupp R, Mason WP, Van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987\u2013996","journal-title":"N Engl J Med"},{"key":"3786_CR2","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1146\/annurev-pathol-012615-044329","volume":"12","author":"S Venneti","year":"2017","unstructured":"Venneti S, Thompson CB (2017) Metabolic reprogramming in brain tumors. Annu Rev Pathol 12:515\u2013545. https:\/\/doi.org\/10.1146\/annurev-pathol-012615-044329","journal-title":"Annu Rev Pathol"},{"key":"3786_CR3","doi-asserted-by":"publisher","first-page":"3437","DOI":"10.1111\/febs.14201","volume":"284","author":"A Rodr\u00edguez-Garc\u00eda","year":"2017","unstructured":"Rodr\u00edguez-Garc\u00eda A, Sams\u00f3 P, Fontova P, Simon-Molas H, Manzano A, Casta\u00f1o E, Rosa JL, Martinez-Outshoorn U, Ventura F, Navarro-Sabat\u00e9 \u00c0, Bartrons R (2017) TGF-\u03b21 targets Smad, p38 MAPK, and PI3K\/Akt signaling pathways to induce PFKFB3 gene expression and glycolysis in glioblastoma cells. Febs j 284:3437\u20133454. doi:https:\/\/doi.org\/10.1111\/febs.14201","journal-title":"Febs j"},{"key":"3786_CR4","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1093\/neuonc\/nov096","volume":"18","author":"Y Gong","year":"2016","unstructured":"Gong Y, Ma Y, Sinyuk M, Loganathan S, Thompson RC, Sarkaria JN, Chen W, Lathia JD, Mobley BC, Clark SW, Wang J (2016) Insulin-mediated signaling promotes proliferation and survival of glioblastoma through Akt activation. Neuro Oncol 18:48\u201357. doi:https:\/\/doi.org\/10.1093\/neuonc\/nov096","journal-title":"Neuro Oncol"},{"key":"3786_CR5","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1016\/j.tranon.2019.04.016","volume":"12","author":"Z Bao","year":"2019","unstructured":"Bao Z, Chen K, Krepel S, Tang P, Gong W, Zhang M, Liang W, Trivett A, Zhou M, Wang JM (2019) High glucose promotes human glioblastoma cell growth by increasing the expression and function of chemoattractant and growth factor receptors. Transl Oncol 12:1155\u20131163. https:\/\/doi.org\/10.1016\/j.tranon.2019.04.016","journal-title":"Transl Oncol"},{"key":"3786_CR6","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1179\/174313209X431101","volume":"32","author":"KL Chaichana","year":"2010","unstructured":"Chaichana KL, McGirt MJ, Woodworth GF, Datoo G, Tamargo RJ, Weingart J, Olivi A, Brem H, Quinones-Hinojosa A (2010) Persistent outpatient hyperglycemia is independently associated with survival, recurrence and malignant degeneration following surgery for hemispheric low grade gliomas. Neurol Res 32:442\u2013448. doi:https:\/\/doi.org\/10.1179\/174313209X431101","journal-title":"Neurol Res"},{"key":"3786_CR7","doi-asserted-by":"publisher","first-page":"1082","DOI":"10.1200\/jco.2008.19.1098","volume":"27","author":"RL Derr","year":"2009","unstructured":"Derr RL, Ye X, Islas MU, Desideri S, Saudek CD, Grossman SA (2009) Association between hyperglycemia and survival in patients with newly diagnosed glioblastoma. J Clin Oncol 27:1082\u20131086. doi:https:\/\/doi.org\/10.1200\/jco.2008.19.1098","journal-title":"J Clin Oncol"},{"key":"3786_CR8","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.clineuro.2018.05.020","volume":"170","author":"VM Lu","year":"2018","unstructured":"Lu VM, Goyal A, Vaughan LS, McDonald KL (2018) The impact of hyperglycemia on survival in glioblastoma: a systematic review and meta-analysis. Clin Neurol Neurosurg 170:165\u2013169. https:\/\/doi.org\/10.1016\/j.clineuro.2018.05.020","journal-title":"Clin Neurol Neurosurg"},{"key":"3786_CR9","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/j.canlet.2014.07.015","volume":"356","author":"TN Seyfried","year":"2015","unstructured":"Seyfried TN, Flores R, Poff AM, D\u2019Agostino DP, Mukherjee P (2015) Metabolic therapy: a new paradigm for managing malignant brain cancer. Cancer Lett 356:289\u2013300. doi:https:\/\/doi.org\/10.1016\/j.canlet.2014.07.015","journal-title":"Cancer Lett"},{"key":"3786_CR10","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1186\/1471-2407-11-315","volume":"11","author":"GD Maurer","year":"2011","unstructured":"Maurer GD, Brucker DP, B\u00e4hr O, Harter PN, Hattingen E, Walenta S, Mueller-Klieser W, Steinbach JP, Rieger J (2011) Differential utilization of ketone bodies by neurons and glioma cell lines: a rationale for ketogenic diet as experimental glioma therapy. BMC Cancer 11:315. doi:https:\/\/doi.org\/10.1186\/1471-2407-11-315","journal-title":"BMC Cancer"},{"key":"3786_CR11","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1126\/science.1227166","volume":"339","author":"T Shimazu","year":"2013","unstructured":"Shimazu T, Hirschey MD, Newman J, He W, Shirakawa K, Le Moan N, Grueter CA, Lim H, Saunders LR, Stevens RD, Newgard CB, Farese RV Jr, de Cabo R, Ulrich S, Akassoglou K, Verdin E (2013) Suppression of oxidative stress by \u03b2-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Science 339:211\u2013214. doi:https:\/\/doi.org\/10.1126\/science.1227166","journal-title":"Science"},{"key":"3786_CR12","doi-asserted-by":"publisher","first-page":"1670","DOI":"10.1158\/1538-7445.AM2016-1670","volume":"76","author":"HB Silva-Nichols","year":"2016","unstructured":"Silva-Nichols HB, Rossi AP, Woolf EC, Fairres MJ, Deleyrolle LP, Reynolds BA, Scheck AC (2016) Abstract 1670: Radiosensitization of glioma cells by the ketone body \u03b2-hydroxybutyrate is associated with enhanced cell cycle arrest in the G2\/M phase. Can Res 76:1670. doi:https:\/\/doi.org\/10.1158\/1538-7445.AM2016-1670","journal-title":"Can Res"},{"key":"3786_CR13","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1080\/09553002.2017.1380330","volume":"95","author":"RJ Klement","year":"2019","unstructured":"Klement RJ (2019) The influence of ketogenic therapy on the 5 R\u2019s of radiobiology. Int J Radiat Biol 95:394\u2013407. doi:https:\/\/doi.org\/10.1080\/09553002.2017.1380330","journal-title":"Int J Radiat Biol"},{"key":"3786_CR14","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1111\/j.1528-1167.2008.01831.x","volume":"49","author":"EH Kossoff","year":"2008","unstructured":"Kossoff EH, Dorward JL (2008) The modified atkins diet. Epilepsia 49:37\u201341. https:\/\/doi.org\/10.1111\/j.1528-1167.2008.01831.x","journal-title":"Epilepsia"},{"key":"3786_CR15","doi-asserted-by":"publisher","first-page":"e36197","DOI":"10.1371\/journal.pone.0036197","volume":"7","author":"MG Abdelwahab","year":"2012","unstructured":"Abdelwahab MG, Fenton KE, Preul MC, Rho JM, Lynch A, Stafford P, Scheck AC (2012) The ketogenic diet is an effective adjuvant to radiation therapy for the treatment of malignant glioma. PLoS One 7:e36197. doi:https:\/\/doi.org\/10.1371\/journal.pone.0036197","journal-title":"PLoS One"},{"key":"3786_CR16","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/1743-7075-4-5","volume":"4","author":"W Zhou","year":"2007","unstructured":"Zhou W, Mukherjee P, Kiebish MA, Markis WT, Mantis JG, Seyfried TN (2007) The calorically restricted ketogenic diet, an effective alternative therapy for malignant brain cancer. Nutr Metab (Lond) 4:5. doi:https:\/\/doi.org\/10.1186\/1743-7075-4-5","journal-title":"Nutr Metab (Lond)"},{"key":"3786_CR17","doi-asserted-by":"publisher","first-page":"e433","DOI":"10.3747\/co.26.4889","volume":"26","author":"C Woodhouse","year":"2019","unstructured":"Woodhouse C, Ward T, Gaskill-Shipley M, Chaudhary R (2019) Feasibility of a modified Atkins diet in glioma patients during radiation and its effect on radiation sensitization. Curr Oncol 26:e433\u2013e438. doi:https:\/\/doi.org\/10.3747\/co.26.4889","journal-title":"Curr Oncol"},{"key":"3786_CR18","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1007\/s11060-014-1362-0","volume":"117","author":"CE Champ","year":"2014","unstructured":"Champ CE, Palmer JD, Volek JS, Werner-Wasik M, Andrews DW, Evans JJ, Glass J, Kim L, Shi W (2014) Targeting metabolism with a ketogenic diet during the treatment of glioblastoma multiforme. Journal of neuro-oncology 117:125\u2013131. doi:https:\/\/doi.org\/10.1007\/s11060-014-1362-0","journal-title":"Journal of neuro-oncology"},{"key":"3786_CR19","doi-asserted-by":"publisher","first-page":"2063","DOI":"10.2337\/diabetes.49.12.2063","volume":"49","author":"RS Hundal","year":"2000","unstructured":"Hundal RS, Krssak M, Dufour S, Laurent D, Lebon V, Chandramouli V, Inzucchi SE, Schumann WC, Petersen KF, Landau BR, Shulman GI (2000) Mechanism by which metformin reduces glucose production in type 2 diabetes. Diabetes 49:2063\u20132069. doi:https:\/\/doi.org\/10.2337\/diabetes.49.12.2063","journal-title":"Diabetes"},{"key":"3786_CR20","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.1177\/009127009603601105","volume":"36","author":"NC Sambol","year":"1996","unstructured":"Sambol NC, Chiang J, O\u2019Conner M, Liu CY, Lin ET, Goodman AM, Benet LZ, Karam JH (1996) Pharmacokinetics and pharmacodynamics of metformin in healthy subjects and patients with noninsulin-dependent diabetes mellitus. J Clin Pharmacol 36:1012\u20131021","journal-title":"J Clin Pharmacol"},{"key":"3786_CR21","doi-asserted-by":"publisher","first-page":"1167","DOI":"10.1172\/jci13505","volume":"108","author":"G Zhou","year":"2001","unstructured":"Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, Wu M, Ventre J, Doebber T, Fujii N, Musi N, Hirshman MF, Goodyear LJ, Moller DE (2001) Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 108:1167\u20131174. doi:https:\/\/doi.org\/10.1172\/jci13505","journal-title":"J Clin Invest"},{"key":"3786_CR22","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1016\/j.cmet.2010.03.014","volume":"11","author":"A Kalender","year":"2010","unstructured":"Kalender A, Selvaraj A, Kim SY, Gulati P, Br\u00fbl\u00e9 S, Viollet B, Kemp BE, Bardeesy N, Dennis P, Schlager JJ, Marette A, Kozma SC, Thomas G (2010) Metformin, independent of AMPK, inhibits mTORC1 in a rag GTPase-dependent manner. Cell Metab 11:390\u2013401. doi:https:\/\/doi.org\/10.1016\/j.cmet.2010.03.014","journal-title":"Cell Metab"},{"key":"3786_CR23","doi-asserted-by":"publisher","first-page":"2184","DOI":"10.1093\/annonc\/mdw410","volume":"27","author":"C Coyle","year":"2016","unstructured":"Coyle C, Cafferty FH, Vale C, Langley RE (2016) Metformin as an adjuvant treatment for cancer: a systematic review and meta-analysis. Ann Oncol 27:2184\u20132195. doi:https:\/\/doi.org\/10.1093\/annonc\/mdw410","journal-title":"Ann Oncol"},{"key":"3786_CR24","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1016\/j.ccell.2019.03.007","volume":"35","author":"M Elgendy","year":"2019","unstructured":"Elgendy M, Cir\u00f2 M, Hosseini A, Weiszmann J, Mazzarella L, Ferrari E, Cazzoli R, Curigliano G, DeCensi A, Bonanni B, Budillon A, Pelicci PG, Janssens V, Ogris M, Baccarini M, Lanfrancone L, Weckwerth W, Foiani M, Minucci S (2019) Combination of hypoglycemia and metformin impairs tumor metabolic plasticity and growth by modulating the PP2A-GSK3\u03b2-MCL-1 axis. Cancer Cell 35:798-815.e795. https:\/\/doi.org\/10.1016\/j.ccell.2019.03.007","journal-title":"Cancer Cell"},{"key":"3786_CR25","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1007\/s11060-014-1602-3","volume":"121","author":"DB G\u00fcrsel","year":"2015","unstructured":"G\u00fcrsel DB, Banu MA, Berry N, Marongiu R, Burkhardt JK, Kobylarz K, Kaplitt MG, Rafii S, Boockvar JA (2015) Tight regulation between cell survival and programmed cell death in GBM stem-like cells by EGFR\/GSK3b\/PP2A signaling. Journal of neuro-oncology 121:19\u201329. doi:https:\/\/doi.org\/10.1007\/s11060-014-1602-3","journal-title":"Journal of neuro-oncology"},{"key":"3786_CR26","doi-asserted-by":"publisher","first-page":"2482","DOI":"10.1158\/1078-0432.CCR-15-0916","volume":"22","author":"RT Martuscello","year":"2016","unstructured":"Martuscello RT, Vedam-Mai V, McCarthy DJ, Schmoll ME, Jundi MA, Louviere CD, Griffith BG, Skinner CL, Suslov O, Deleyrolle LP, Reynolds BA (2016) A supplemented high-fat low-carbohydrate diet for the treatment of glioblastoma. Clin Cancer Res 22:2482. https:\/\/doi.org\/10.1158\/1078-0432.CCR-15-0916","journal-title":"Clin Cancer Res"},{"key":"3786_CR27","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1093\/ajcn\/44.5.630","volume":"44","author":"TB Seaton","year":"1986","unstructured":"Seaton TB, Welle SL, Warenko MK, Campbell RG (1986) Thermic effect of medium-chain and long-chain triglycerides in man. Am J Clin Nutr 44:630\u2013634. https:\/\/doi.org\/10.1093\/ajcn\/44.5.630","journal-title":"Am J Clin Nutr"},{"key":"3786_CR28","unstructured":"Tzameret software on consumption of food and nutrients.2016"},{"key":"3786_CR29","doi-asserted-by":"publisher","first-page":"3048","DOI":"10.1200\/jco.2009.25.6941","volume":"28","author":"SE Fogh","year":"2010","unstructured":"Fogh SE, Andrews DW, Glass J, Curran W, Glass C, Champ C, Evans JJ, Hyslop T, Pequignot E, Downes B, Comber E, Maltenfort M, Dicker AP, Werner-Wasik M (2010) Hypofractionated stereotactic radiation therapy: an effective therapy for recurrent high-grade gliomas. J Clin Oncol 28:3048\u20133053. doi:https:\/\/doi.org\/10.1200\/jco.2009.25.6941","journal-title":"J Clin Oncol"},{"key":"3786_CR30","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1093\/neuonc\/nou230","volume":"17","author":"L Zach","year":"2015","unstructured":"Zach L, Guez D, Last D, Daniels D, Grober Y, Nissim O, Hoffmann C, Nass D, Talianski A, Spiegelmann R, Tsarfaty G, Salomon S, Hadani M, Kanner A, Blumenthal DT, Bukstein F, Yalon M, Zauberman J, Roth J, Shoshan Y, Fridman E, Wygoda M, Limon D, Tzuk T, Cohen ZR, Mardor Y (2015) Delayed contrast extravasation MRI: a new paradigm in neuro-oncology. Neurooncology 17:457\u2013465. doi:https:\/\/doi.org\/10.1093\/neuonc\/nou230","journal-title":"Neurooncology"},{"key":"3786_CR31","doi-asserted-by":"publisher","first-page":"2572","DOI":"10.1200\/JCO.1999.17.8.2572","volume":"17","author":"ET Wong","year":"1999","unstructured":"Wong ET, Hess KR, Gleason MJ, Jaeckle KA, Kyritsis AP, Prados MD, Levin VA, Yung WKA (1999) Outcomes and prognostic factors in recurrent glioma patients enrolled onto phase II clinical trials. J Clin Oncol 17:2572\u20132572. https:\/\/doi.org\/10.1200\/JCO.1999.17.8.2572","journal-title":"J Clin Oncol"},{"key":"3786_CR32","doi-asserted-by":"publisher","first-page":"e0180457","DOI":"10.1371\/journal.pone.0180457","volume":"12","author":"KA Kessel","year":"2017","unstructured":"Kessel KA, Hesse J, Straube C, Zimmer C, Schmidt-Graf F, Schlegel J, Meyer B, Combs SE (2017) Modification and optimization of an established prognostic score after re-irradiation of recurrent glioma. PLoS ONE 12:e0180457. https:\/\/doi.org\/10.1371\/journal.pone.0180457","journal-title":"PLoS ONE"},{"key":"3786_CR33","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.1093\/jn\/nxy119","volume":"148","author":"CW Cohen","year":"2018","unstructured":"Cohen CW, Fontaine KR, Arend RC, Alvarez RD, Leath Iii CA, Huh WK, Bevis KS, Kim KH, Straughn JM Jr, Gower BA (2018) A ketogenic diet reduces central obesity and serum insulin in women with ovarian or endometrial cancer. J Nutr 148:1253\u20131260. https:\/\/doi.org\/10.1093\/jn\/nxy119","journal-title":"J Nutr"},{"key":"3786_CR34","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1186\/s13058-020-01331-5","volume":"22","author":"RJ Klement","year":"2020","unstructured":"Klement RJ, Champ CE, K\u00e4mmerer U, Koebrunner PS, Krage K, Sch\u00e4fer G, Weigel M, Sweeney RA (2020) Impact of a ketogenic diet intervention during radiotherapy on body composition: III-final results of the KETOCOMP study for breast cancer patients. Breast Cancer Res 22:94. doi:https:\/\/doi.org\/10.1186\/s13058-020-01331-5","journal-title":"Breast Cancer Res"},{"key":"3786_CR35","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1007\/s12032-020-1337-2","volume":"37","author":"RJ Klement","year":"2020","unstructured":"Klement RJ, Brehm N, Sweeney RA (2020) Ketogenic diets in medical oncology: a systematic review with focus on clinical outcomes. Med Oncol 37:14. doi:https:\/\/doi.org\/10.1007\/s12032-020-1337-2","journal-title":"Med Oncol"},{"key":"3786_CR36","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1038\/s42003-019-0455-x","volume":"2","author":"P Mukherjee","year":"2019","unstructured":"Mukherjee P, Augur ZM, Li M, Hill C, Greenwood B, Domin MA, Kondakci G, Narain NR, Kiebish MA, Bronson RT, Arismendi-Morillo G, Chinopoulos C, Seyfried TN (2019) Therapeutic benefit of combining calorie-restricted ketogenic diet and glutamine targeting in late-stage experimental glioblastoma. Communications Biology 2:200. doi:https:\/\/doi.org\/10.1038\/s42003-019-0455-x","journal-title":"Communications Biology"},{"key":"3786_CR37","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1111\/j.1528-1167.2008.01853.x","volume":"49","author":"TN Seyfried","year":"2008","unstructured":"Seyfried TN, Kiebish M, Mukherjee P, Marsh J (2008) Targeting energy metabolism in brain cancer with calorically restricted ketogenic diets. Epilepsia 49:114\u2013116. doi:https:\/\/doi.org\/10.1111\/j.1528-1167.2008.01853.x","journal-title":"Epilepsia"},{"key":"3786_CR38","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.cmet.2007.10.002","volume":"7","author":"RJ DeBerardinis","year":"2008","unstructured":"DeBerardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB (2008) The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab 7:11\u201320. https:\/\/doi.org\/10.1016\/j.cmet.2007.10.002","journal-title":"Cell Metab"},{"key":"3786_CR39","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/j.molcel.2019.07.007","volume":"76","author":"X Wang","year":"2019","unstructured":"Wang X, Liu R, Qu X, Yu H, Chu H, Zhang Y, Zhu W, Wu X, Gao H, Tao B, Li W, Liang J, Li G, Yang W (2019) \u03b1-ketoglutarate-activated NF-\u03baB signaling promotes compensatory glucose uptake and brain tumor development. Molecular cell 76:148-162.e147. https:\/\/doi.org\/10.1016\/j.molcel.2019.07.007","journal-title":"Molecular cell"},{"key":"3786_CR40","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1093\/neuonc\/now088","volume":"18","author":"HM De Feyter","year":"2016","unstructured":"De Feyter HM, Behar KL, Rao JU, Madden-Hennessey K, Ip KL, Hyder F, Drewes LR, Geschwind JF, de Graaf RA, Rothman DL (2016) A ketogenic diet increases transport and oxidation of ketone bodies in RG2 and 9L gliomas without affecting tumor growth. Neuro Oncol 18:1079\u20131087. doi:https:\/\/doi.org\/10.1093\/neuonc\/now088","journal-title":"Neuro Oncol"},{"key":"3786_CR41","doi-asserted-by":"publisher","first-page":"101453","DOI":"10.1016\/j.isci.2020.101453","volume":"23","author":"J Sperry","year":"2020","unstructured":"Sperry J, Condro MC, Guo L, Braas D, Vanderveer-Harris N, Kim KK, Pope WB, Divakaruni AS, Lai A, Christofk H (2020) Glioblastoma utilizes fatty acids and ketone bodies for growth allowing progression during ketogenic diet therapy. Iscience 23:101453","journal-title":"Iscience"},{"key":"3786_CR42","doi-asserted-by":"publisher","first-page":"190099","DOI":"10.1098\/rsob.190099","volume":"9","author":"D Vara-Ciruelos","year":"2019","unstructured":"Vara-Ciruelos D, Russell FM, Hardie DG (2019) The strange case of AMPK and cancer: Dr Jekyll or Mr Hyde? (\u2020). Open Biol 9:190099. doi:https:\/\/doi.org\/10.1098\/rsob.190099","journal-title":"Open Biol"},{"key":"3786_CR43","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1038\/s41419-019-1452-1","volume":"10","author":"S Zhang","year":"2019","unstructured":"Zhang S, Sheng H, Zhang X, Qi Q, Chan CB, Li L, Shan C, Ye K (2019) Cellular energy stress induces AMPK-mediated regulation of glioblastoma cell proliferation by PIKE-A phosphorylation. Cell Death Dis 10:222. doi:https:\/\/doi.org\/10.1038\/s41419-019-1452-1","journal-title":"Cell Death Dis"},{"key":"3786_CR44","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaw5473","author":"B Faubert","year":"2020","unstructured":"Faubert B, Solmonson A, DeBerardinis RJ (2020) Metabolic reprogramming and cancer progression. Science 368. doi:https:\/\/doi.org\/10.1126\/science.aaw5473","journal-title":"Science 368"},{"key":"3786_CR45","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.1016\/j.chembiol.2017.08.028","volume":"24","author":"A Luengo","year":"2017","unstructured":"Luengo A, Gui DY, Vander Heiden MG (2017) Targeting metabolism for cancer therapy. Cell Chem Biol 24:1161\u20131180. https:\/\/doi.org\/10.1016\/j.chembiol.2017.08.028","journal-title":"Cell Chem Biol"},{"key":"3786_CR46","doi-asserted-by":"publisher","first-page":"e108444","DOI":"10.1371\/journal.pone.0108444","volume":"9","author":"Y Zhuang","year":"2014","unstructured":"Zhuang Y, Chan DK, Haugrud AB, Miskimins WK (2014) Mechanisms by which low glucose enhances the cytotoxicity of metformin to cancer cells both in vitro and in vivo. PLoS One 9:e108444. doi:https:\/\/doi.org\/10.1371\/journal.pone.0108444","journal-title":"PLoS One"},{"key":"3786_CR47","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.mehy.2011.04.001","volume":"77","author":"J Oleksyszyn","year":"2011","unstructured":"Oleksyszyn J (2011) The complete control of glucose level utilizing the composition of ketogenic diet with the gluconeogenesis inhibitor, the anti-diabetic drug metformin, as a potential anti-cancer therapy. Medical hypotheses 77:171\u2013173. doi:https:\/\/doi.org\/10.1016\/j.mehy.2011.04.001","journal-title":"Medical hypotheses"},{"key":"3786_CR48","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1016\/s0006-2952(01)00679-7","volume":"62","author":"JP Fulgencio","year":"2001","unstructured":"Fulgencio JP, Kohl C, Girard J, P\u00e9gorier JP (2001) Effect of metformin on fatty acid and glucose metabolism in freshly isolated hepatocytes and on specific gene expression in cultured hepatocytes. Biochem Pharmacol 62:439\u2013446. doi:https:\/\/doi.org\/10.1016\/s0006-2952(01)00679-7","journal-title":"Biochem Pharmacol"},{"key":"3786_CR49","doi-asserted-by":"publisher","DOI":"10.1177\/1759091414550997","author":"S Takahashi","year":"2014","unstructured":"Takahashi S, Iizumi T, Mashima K, Abe T, Suzuki N (2014) Roles and regulation of ketogenesis in cultured astroglia and neurons under hypoxia and hypoglycemia. ASN Neuro. https:\/\/doi.org\/10.1177\/1759091414550997","journal-title":"ASN Neuro"},{"key":"3786_CR50","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1038\/s41574-019-0242-2","volume":"15","author":"M Foretz","year":"2019","unstructured":"Foretz M, Guigas B, Viollet B (2019) Understanding the glucoregulatory mechanisms of metformin in type 2 diabetes mellitus. Nat Rev Endocrinol 15:569\u2013589. https:\/\/doi.org\/10.1038\/s41574-019-0242-2","journal-title":"Nat Rev Endocrinol"}],"container-title":["Journal of Neuro-Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11060-021-03786-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11060-021-03786-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11060-021-03786-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T14:17:56Z","timestamp":1626272276000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11060-021-03786-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,21]]},"references-count":50,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2021,7]]}},"alternative-id":["3786"],"URL":"https:\/\/doi.org\/10.1007\/s11060-021-03786-8","relation":{},"ISSN":["0167-594X","1573-7373"],"issn-type":[{"value":"0167-594X","type":"print"},{"value":"1573-7373","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,21]]},"assertion":[{"value":"8 May 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 June 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 June 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Yaacov Lawrence: Research funding: Karyopharm Therapeutics, Checkmate Pharmaceuticals, Bristol-Myers Squibb and pending from Merck Serono. Honoria\/consultancy fees: Bristol-Myers Squibb, Clinigen Group and Roche Genetech. Stock ownership: Protean Biodiagnostics Inc. Colin E. Champ receives compensation for his dietary books, Leor Zach is an advisor of Trail-IN Pharma. Scientific advisory board for Atkins, and scientific advisory board for Biosense. The other authors declare that they have no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This study was performed in line with the principles of the Declaration of Helsinki. The trial was approved by the local Institutional Review Board (IRB) - SMC 0712\u2009\u2212\u200913, and registered on Clinicaltrials.gov NCT02149459.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"All patients signed an IRB approved informed consent form, in accordance with the principals of Good Clinical Practice (GCP).","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}}]}}