{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:17:37Z","timestamp":1790641057610,"version":"4.1.0"},"reference-count":89,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T00:00:00Z","timestamp":1616371200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004622","name":"KWF Kankerbestrijding","doi-asserted-by":"publisher","award":["UVA 2014-6839 and UVA 2016.1-10460"],"award-info":[{"award-number":["UVA 2014-6839 and UVA 2016.1-10460"]}],"id":[{"id":"10.13039\/501100004622","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004329","name":"Slovenian Research Agency","doi-asserted-by":"publisher","award":["Project J3-2526 and project Z3-1870"],"award-info":[{"award-number":["Project J3-2526 and project Z3-1870"]}],"id":[{"id":"10.13039\/501100004329","id-type":"DOI","asserted-by":"publisher"}]},{"name":"IVY Interreg Fellowship","award":["2018"],"award-info":[{"award-number":["2018"]}]},{"name":"the Fondation pour la Recherche Nuovo-Soldati","award":["2019"],"award-info":[{"award-number":["2019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Cancer is a redox disease. Low levels of reactive oxygen species (ROS) are beneficial for cells and have anti-cancer effects. ROS are produced in the mitochondria during ATP production by oxidative phosphorylation (OXPHOS). In the present review, we describe ATP production in primary brain tumors, glioblastoma, in relation to ROS production. Differentiated glioblastoma cells mainly use glycolysis for ATP production (aerobic glycolysis) without ROS production, whereas glioblastoma stem cells (GSCs) in hypoxic periarteriolar niches use OXPHOS for ATP and ROS production, which is modest because of the hypoxia and quiescence of GSCs. In a significant proportion of glioblastoma, isocitrate dehydrogenase 1 (IDH1) is mutated, causing metabolic rewiring, and all cancer cells use OXPHOS for ATP and ROS production. Systemic therapeutic inhibition of glycolysis is not an option as clinical trials have shown ineffectiveness or unwanted side effects. We argue that systemic therapeutic inhibition of OXPHOS is not an option either because the anti-cancer effects of ROS production in healthy cells is inhibited as well. Therefore, we advocate to remove GSCs out of their hypoxic niches by the inhibition of their binding to niches to enable their differentiation and thus increase their sensitivity to radiotherapy and\/or chemotherapy.<\/jats:p>","DOI":"10.3390\/cells10030705","type":"journal-article","created":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T12:55:07Z","timestamp":1616417707000},"page":"705","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Energy Metabolism in IDH1 Wild-Type and IDH1-Mutated Glioblastoma Stem Cells: A Novel Target for Therapy?"],"prefix":"10.3390","volume":"10","author":[{"given":"Cornelis J.F.","family":"van Noorden","sequence":"first","affiliation":[{"name":"Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Ve\u010dna Pot 111, 1000 Ljubljana, Slovenia"},{"name":"Department of Medical Biology, Amsterdam UMC Location Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vashendriya V.V.","family":"Hira","sequence":"additional","affiliation":[{"name":"Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Ve\u010dna Pot 111, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2246-1460","authenticated-orcid":false,"given":"Amber J.","family":"van Dijck","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Amsterdam UMC Location Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Metka","family":"Novak","sequence":"additional","affiliation":[{"name":"Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Ve\u010dna Pot 111, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0247-5811","authenticated-orcid":false,"given":"Barbara","family":"Breznik","sequence":"additional","affiliation":[{"name":"Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Ve\u010dna Pot 111, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5651-3997","authenticated-orcid":false,"given":"Remco J.","family":"Molenaar","sequence":"additional","affiliation":[{"name":"Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Ve\u010dna Pot 111, 1000 Ljubljana, Slovenia"},{"name":"Department of Medical Oncology, Amsterdam UMC Location Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/S0140-6736(13)62365-X","article-title":"Type 2 diabetes as a redox disease","volume":"383","author":"Watson","year":"2014","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1016\/S0140-6736(14)61485-9","article-title":"Type 2 diabetes and cancer as redox diseases?","volume":"384","author":"Molenaar","year":"2014","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1503\/cmaj.051351","article-title":"Health benefits of physical activity: The evidence","volume":"174","author":"Warburton","year":"2006","journal-title":"Can. 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