{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:48:45Z","timestamp":1791319725446,"version":"4.3.1"},"reference-count":90,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T00:00:00Z","timestamp":1625529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Teo Foundation","award":["Research Fellowship"],"award-info":[{"award-number":["Research Fellowship"]}]},{"DOI":"10.13039\/501100006641","name":"Cure Brain Cancer Foundation","doi-asserted-by":"publisher","award":["Early Career Fellowship"],"award-info":[{"award-number":["Early Career Fellowship"]}],"id":[{"id":"10.13039\/501100006641","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008221","name":"Cure Starts Now Foundation","doi-asserted-by":"publisher","award":["Grant"],"award-info":[{"award-number":["Grant"]}],"id":[{"id":"10.13039\/100008221","id-type":"DOI","asserted-by":"publisher"}]},{"name":"DIPG Collaborative Project Grant","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"name":"Mark Hughes Foundation Innovation Grant","award":["HMRI 17-25"],"award-info":[{"award-number":["HMRI 17-25"]}]},{"name":"Mark Hughes Foundation","award":["Matt Callander \u2018Beanie for Brain Cancer\u2019 Hunter Medical Research Institute Fellowship"],"award-info":[{"award-number":["Matt Callander \u2018Beanie for Brain Cancer\u2019 Hunter Medical Research Institute Fellowship"]}]},{"name":"Sydney West Radiation Oncology Network","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"name":"Westmead Charitable Trust Grant","award":["NA"],"award-info":[{"award-number":["NA"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>As the cornerstone of high-grade glioma (HGG) treatment, radiotherapy temporarily controls tumor cells via inducing oxidative stress and subsequent DNA breaks. However, almost all HGGs recur within months. Therefore, it is important to understand the underlying mechanisms of radioresistance, so that novel strategies can be developed to improve the effectiveness of radiotherapy. While currently poorly understood, radioresistance appears to be predominantly driven by altered metabolism and hypoxia. Glucose is a central macronutrient, and its metabolism is rewired in HGG cells, increasing glycolytic flux to produce energy and essential metabolic intermediates, known as the Warburg effect. This altered metabolism in HGG cells not only supports cell proliferation and invasiveness, but it also contributes significantly to radioresistance. Several metabolic drugs have been used as a novel approach to improve the radiosensitivity of HGGs, including dichloroacetate (DCA), a small molecule used to treat children with congenital mitochondrial disorders. DCA reverses the Warburg effect by inhibiting pyruvate dehydrogenase kinases, which subsequently activates mitochondrial oxidative phosphorylation at the expense of glycolysis. This effect is thought to block the growth advantage of HGGs and improve the radiosensitivity of HGG cells. This review highlights the main features of altered glucose metabolism in HGG cells as a contributor to radioresistance and describes the mechanism of action of DCA. Furthermore, we will summarize recent advances in DCA\u2019s pre-clinical and clinical studies as a radiosensitizer and address how these scientific findings can be translated into clinical practice to improve the management of HGG patients.<\/jats:p>","DOI":"10.3390\/ijms22147265","type":"journal-article","created":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T11:36:44Z","timestamp":1625571404000},"page":"7265","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Targeting Glucose Metabolism of Cancer Cells with Dichloroacetate to Radiosensitize High-Grade Gliomas"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0503-7166","authenticated-orcid":false,"given":"Kristina M.","family":"Cook","sequence":"first","affiliation":[{"name":"Charles Perkins Centre, Faculty of Medicine and Health, University of Sydney, Sydney 2006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2435-2150","authenticated-orcid":false,"given":"Han","family":"Shen","sequence":"additional","affiliation":[{"name":"Charles Perkins Centre, Faculty of Medicine and Health, University of Sydney, Sydney 2006, Australia"},{"name":"Translational Radiation Biology and Oncology Laboratory, Centre for Cancer Research, Westmead Institute for Medical Research, Westmead 2145, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4923-791X","authenticated-orcid":false,"given":"Kelly J.","family":"McKelvey","sequence":"additional","affiliation":[{"name":"Charles Perkins Centre, Faculty of Medicine and Health, University of Sydney, Sydney 2006, Australia"},{"name":"Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, Faculty of Medicine and Health, University of Sydney, St. Leonards 2065, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harriet E.","family":"Gee","sequence":"additional","affiliation":[{"name":"Charles Perkins Centre, Faculty of Medicine and Health, University of Sydney, Sydney 2006, Australia"},{"name":"Translational Radiation Biology and Oncology Laboratory, Centre for Cancer Research, Westmead Institute for Medical Research, Westmead 2145, Australia"},{"name":"Sydney West Radiation Oncology Network, University of Sydney, Sydney 2006, Australia"},{"name":"Children\u2019s Medical Research Institute, Westmead 2145, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Hau","sequence":"additional","affiliation":[{"name":"Charles Perkins Centre, Faculty of Medicine and Health, University of Sydney, Sydney 2006, Australia"},{"name":"Translational Radiation Biology and Oncology Laboratory, Centre for Cancer Research, Westmead Institute for Medical Research, Westmead 2145, Australia"},{"name":"Sydney West Radiation Oncology Network, University of Sydney, Sydney 2006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"313","DOI":"10.3109\/02688697.2015.1119242","article-title":"Combination of 5-ALA and iMRI in re-resection of recurrent glioblastoma","volume":"30","author":"Lescher","year":"2016","journal-title":"Br. 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