{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T11:21:00Z","timestamp":1783164060994,"version":"3.54.6"},"reference-count":45,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004622","name":"KWF Dutch Cancer Society","doi-asserted-by":"publisher","award":["13741"],"award-info":[{"award-number":["13741"]}],"id":[{"id":"10.13039\/501100004622","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","thegreenjournal.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Radiotherapy and Oncology"],"published-print":{"date-parts":[[2026,8]]},"DOI":"10.1016\/j.radonc.2026.111617","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T16:14:20Z","timestamp":1780503260000},"page":"111617","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Mitochondria-targeted OXPHOS inhibition enhances radiotherapy efficacy by disrupting mitochondrial function"],"prefix":"10.1016","volume":"221","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4930-1742","authenticated-orcid":false,"given":"Anne P.M.","family":"Beerkens","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo S.","family":"Taracatac","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1143-5472","authenticated-orcid":false,"given":"Wenny J.M.","family":"Peeters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes P.W.","family":"Peters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gosse J.","family":"Adema","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7250-0846","authenticated-orcid":false,"given":"Sandra","family":"Heskamp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5751-4796","authenticated-orcid":false,"given":"Johan","family":"Bussink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1930-6638","authenticated-orcid":false,"given":"Paul N.","family":"Span","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"6","key":"10.1016\/j.radonc.2026.111617_b0005","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1002\/cncr.21324","article-title":"The role of radiotherapy in cancer treatment: estimating optimal utilization from a review of evidence-based clinical guidelines","volume":"104","author":"Delaney","year":"2005","journal-title":"Cancer"},{"issue":"1152","key":"10.1016\/j.radonc.2026.111617_b0010","doi-asserted-by":"crossref","DOI":"10.1259\/bjr.20230334","article-title":"The use of radiotherapy, surgery and chemotherapy in the curative treatment of cancer: results from the FORTY (Favourable Outcomes from RadioTherapY) project","volume":"96","author":"Mee","year":"2023","journal-title":"Br J Radiol"},{"issue":"13","key":"10.1016\/j.radonc.2026.111617_b0015","doi-asserted-by":"crossref","DOI":"10.3390\/ijms20133212","article-title":"Tumor microenvironment as a \u201cgame changer\u201d in cancer radiotherapy","volume":"20","author":"Jarosz-Biej","year":"2019","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.radonc.2026.111617_b0020","series-title":"Basic clinical radiobiology","author":"Joiner","year":"2018"},{"issue":"4","key":"10.1016\/j.radonc.2026.111617_b0025","article-title":"A mechanistic investigation of the oxygen fixation hypothesis and oxygen enhancement ratio","volume":"1","author":"Grimes","year":"2015","journal-title":"Biomed Phys Eng Express"},{"issue":"2","key":"10.1016\/j.radonc.2026.111617_b0030","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1053\/j.semnuclmed.2014.10.002","article-title":"Biology of hypoxia","volume":"45","author":"Span","year":"2015","journal-title":"Semin Nucl Med"},{"issue":"3","key":"10.1016\/j.radonc.2026.111617_b0035","doi-asserted-by":"crossref","first-page":"313","DOI":"10.3109\/02841869509093981","article-title":"Analysis of the effects of oxygen supply and demand on hypoxic fraction in tumors","volume":"34","author":"Secomb","year":"1995","journal-title":"Acta Oncol"},{"key":"10.1016\/j.radonc.2026.111617_b0040","doi-asserted-by":"crossref","first-page":"12308","DOI":"10.1038\/ncomms12308","article-title":"The anti-malarial atovaquone increases radiosensitivity by alleviating tumour hypoxia","volume":"7","author":"Ashton","year":"2016","journal-title":"Nat Commun"},{"issue":"24","key":"10.1016\/j.radonc.2026.111617_b0045","doi-asserted-by":"crossref","first-page":"5263","DOI":"10.1158\/1078-0432.CCR-22-1665","article-title":"A phase II randomized trial of chemoradiation with or without metformin in locally advanced cervical cancer","volume":"28","author":"Han","year":"2022","journal-title":"Clin Cancer Res"},{"issue":"9","key":"10.1016\/j.radonc.2026.111617_b0050","doi-asserted-by":"crossref","first-page":"2459","DOI":"10.1158\/1078-0432.CCR-20-4128","article-title":"Mitochondrial inhibitor atovaquone increases tumor oxygenation and inhibits hypoxic gene expression in patients with non-small cell lung cancer","volume":"27","author":"Skwarski","year":"2021","journal-title":"Clin Cancer Res"},{"issue":"1","key":"10.1016\/j.radonc.2026.111617_b0055","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/s41591-022-02103-8","article-title":"Complex I inhibitor of oxidative phosphorylation in advanced solid tumors and acute myeloid leukemia: phase I trials","volume":"29","author":"Yap","year":"2023","journal-title":"Nat Med"},{"issue":"15","key":"10.1016\/j.radonc.2026.111617_b0060","doi-asserted-by":"crossref","first-page":"10043","DOI":"10.1021\/acs.chemrev.7b00042","article-title":"Mitochondria-targeted triphenylphosphonium-based compounds: syntheses, mechanisms of action, and therapeutic and diagnostic applications","volume":"117","author":"Zielonka","year":"2017","journal-title":"Chem Rev"},{"issue":"7","key":"10.1016\/j.radonc.2026.111617_b0065","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1158\/1078-0432.CCR-24-3296","article-title":"Mitochondria targeting of oxidative phosphorylation inhibitors to alleviate hypoxia and enhance anticancer treatment efficacy","volume":"31","author":"Beerkens","year":"2025","journal-title":"Clin Cancer Res"},{"issue":"25","key":"10.1016\/j.radonc.2026.111617_b0070","doi-asserted-by":"crossref","first-page":"13844","DOI":"10.1016\/S0021-9258(17)38802-6","article-title":"Mitochondrial and plasma membrane potentials cause unusual accumulation and retention of rhodamine 123 by human breast adenocarcinoma-derived MCF-7 cells","volume":"260","author":"Davis","year":"1985","journal-title":"J Biol Chem"},{"issue":"16","key":"10.1016\/j.radonc.2026.111617_b0075","first-page":"4361","article-title":"Basis for the selective cytotoxicity of rhodamine 123","volume":"47","author":"Modica-Napolitano","year":"1987","journal-title":"Cancer Res"},{"issue":"17","key":"10.1016\/j.radonc.2026.111617_b0080","doi-asserted-by":"crossref","first-page":"5292","DOI":"10.1073\/pnas.79.17.5292","article-title":"Unusual retention of rhodamine 123 by mitochondria in muscle and carcinoma cells","volume":"79","author":"Summerhayes","year":"1982","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"10.1016\/j.radonc.2026.111617_b0085","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s40170-024-00342-6","article-title":"Characterizing OXPHOS inhibitor-mediated alleviation of hypoxia using high-throughput live cell-imaging","volume":"12","author":"Beerkens","year":"2024","journal-title":"Cancer Metab"},{"issue":"51","key":"10.1016\/j.radonc.2026.111617_b0090","doi-asserted-by":"crossref","first-page":"48332","DOI":"10.1021\/acsomega.2c06525","article-title":"Stability of phenyl-modified triphenylphosphonium conjugates and interactions with DTPA","volume":"7","author":"Gruenwald","year":"2022","journal-title":"ACS Omega"},{"issue":"1","key":"10.1016\/j.radonc.2026.111617_b0095","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1021\/acs.jmedchem.0c01671","article-title":"A novel triphenylphosphonium carrier to target mitochondria without uncoupling oxidative phosphorylation","volume":"64","author":"Kulkarni","year":"2021","journal-title":"J Med Chem"},{"issue":"23","key":"10.1016\/j.radonc.2026.111617_b0100","doi-asserted-by":"crossref","first-page":"34084","DOI":"10.18632\/oncotarget.9122","article-title":"Repurposing atovaquone: targeting mitochondrial complex III and OXPHOS to eradicate cancer stem cells","volume":"7","author":"Fiorillo","year":"2016","journal-title":"Oncotarget"},{"issue":"2","key":"10.1016\/j.radonc.2026.111617_b0105","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1089\/ars.2016.6677","article-title":"Selective disruption of respiratory supercomplexes as a new strategy to suppress Her2high Breast Cancer","volume":"26","author":"Rohlenova","year":"2017","journal-title":"Antioxid Redox Sign"},{"issue":"11","key":"10.1016\/j.radonc.2026.111617_b0110","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1002\/mc.23603","article-title":"Mitochondria-targeted metformin (mitomet) inhibits lung cancer in cellular models and in mice by enhancing the generation of reactive oxygen species","volume":"62","author":"Shameem","year":"2023","journal-title":"Mol Carcinog"},{"issue":"1","key":"10.1016\/j.radonc.2026.111617_b0115","doi-asserted-by":"crossref","DOI":"10.1186\/s40170-023-00304-4","article-title":"Tamoxifen induces radioresistance through NRF2-mediated metabolic reprogramming in breast cancer","volume":"11","author":"Reinema","year":"2023","journal-title":"Cancer Metab"},{"key":"10.1016\/j.radonc.2026.111617_b0120","article-title":"MitoTam induces ferroptosis and increases radiosensitivity in head and neck cancer cells","volume":"110503","author":"Reinema","year":"2024","journal-title":"Radiother Oncol"},{"issue":"7","key":"10.1016\/j.radonc.2026.111617_b0125","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1038\/nm0795-649","article-title":"Targeting antigen into the phagocytic pathway in vivo induces protective tumour immunity","volume":"1","author":"Falo","year":"1995","journal-title":"Nat Med"},{"issue":"5","key":"10.1016\/j.radonc.2026.111617_b0130","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1007\/s11307-024-01934-w","article-title":"MHC-I and PD-L1 expression is associated with decreased tumor outgrowth and is radiotherapy-inducible in the murine head and neck squamous cell carcinoma model MOC1","volume":"26","author":"Boreel","year":"2024","journal-title":"Mol Imaging Biol"},{"key":"10.1016\/j.radonc.2026.111617_b0135","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1007\/978-1-0716-3056-3_17","article-title":"Cell viability assay with 3D prostate tumor spheroids","volume":"2645","author":"Oner","year":"2023","journal-title":"Methods Mol Biol"},{"key":"10.1016\/j.radonc.2026.111617_b0140","article-title":"Inhibition of OXPHOS induces metabolic rewiring and reduces hypoxia in murine tumor models","author":"Boreel","year":"2024","journal-title":"Clin Transl Radiat Oncol"},{"issue":"3","key":"10.1016\/j.radonc.2026.111617_b0145","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.radonc.2013.06.037","article-title":"The PERK\/ATF4\/LAMP3-arm of the unfolded protein response affects radioresistance by interfering with the DNA damage response","volume":"108","author":"Nagelkerke","year":"2013","journal-title":"Radiother Oncol"},{"issue":"11","key":"10.1016\/j.radonc.2026.111617_b0150","doi-asserted-by":"crossref","first-page":"2970","DOI":"10.1158\/1078-0432.CCR-20-3913","article-title":"Targeting oxidative phosphorylation to increase the efficacy of radio- and immune-combination therapy","volume":"27","author":"Boreel","year":"2021","journal-title":"Clin Cancer Res"},{"issue":"2","key":"10.1016\/j.radonc.2026.111617_b0155","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1089\/ars.2016.6677","article-title":"Selective disruption of respiratory supercomplexes as a new strategy to suppress Her2(high) breast cancer","volume":"26","author":"Rohlenova","year":"2017","journal-title":"Antioxid Redox Sign"},{"issue":"3","key":"10.1016\/j.radonc.2026.111617_b0160","doi-asserted-by":"crossref","DOI":"10.1002\/ctm2.645","article-title":"Simultaneous targeting of mitochondrial metabolism and immune checkpoints as a new strategy for renal cancer therapy","volume":"12","author":"Stemberkova-Hubackova","year":"2022","journal-title":"Clin Transl Med"},{"key":"10.1016\/j.radonc.2026.111617_b0165","doi-asserted-by":"crossref","DOI":"10.1016\/j.eclinm.2023.101873","article-title":"Mitochondrially targeted tamoxifen in patients with metastatic solid tumours: an open-label, phase I\/Ib single-centre trial","volume":"57","author":"Bielcikova","year":"2023","journal-title":"EClinicalMedicine"},{"issue":"1","key":"10.1016\/j.radonc.2026.111617_b0170","article-title":"Combining PEGylated mito-atovaquone with MCT and Krebs cycle redox inhibitors as a potential strategy to abrogate tumor cell proliferation","volume":"12","author":"Cheng","year":"2022","journal-title":"Sci Rep-Uk"},{"issue":"20","key":"10.1016\/j.radonc.2026.111617_b0175","doi-asserted-by":"crossref","first-page":"5585","DOI":"10.1158\/1078-0432.CCR-12-0858","article-title":"Targeting hypoxia, HIF-1, and tumor glucose metabolism to improve radiotherapy efficacy","volume":"18","author":"Meijer","year":"2012","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.radonc.2026.111617_b0180","article-title":"Antioxidative stress: inhibiting reactive oxygen species production as a cause of radioresistance and chemoresistance","author":"Chen","year":"2021","journal-title":"Oxid Med Cell Longev"},{"issue":"4","key":"10.1016\/j.radonc.2026.111617_b0185","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0121837","article-title":"Lipophilic triphenylphosphonium cations inhibit mitochondrial electron transport chain and induce mitochondrial proton leak","volume":"10","author":"Trnka","year":"2015","journal-title":"PLoS One"},{"issue":"1","key":"10.1016\/j.radonc.2026.111617_b0190","doi-asserted-by":"crossref","DOI":"10.1007\/s00432-023-05515-2","article-title":"Mitophagy plays a \u201cdouble-edged sword\u201d role in the radiosensitivity of cancer cells","volume":"150","author":"Wang","year":"2024","journal-title":"J Cancer Res Clin"},{"issue":"1","key":"10.1016\/j.radonc.2026.111617_b0195","first-page":"42","article-title":"Effects of different doses of X-ray irradiation on cell apoptosis, cell cycle, DNA damage repair and glycolysis in HeLa cells","volume":"17","author":"Zhao","year":"2019","journal-title":"Oncol Lett"},{"issue":"5","key":"10.1016\/j.radonc.2026.111617_b0200","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.3892\/ijo.2017.3924","article-title":"2-Methoxyestradiol enhances radiosensitivity in radioresistant melanoma MDA-MB-435R cells by regulating glycolysis via HIF-1alpha\/PDK1 axis","volume":"50","author":"Zhao","year":"2017","journal-title":"Int J Oncol"},{"issue":"20","key":"10.1016\/j.radonc.2026.111617_b0205","doi-asserted-by":"crossref","DOI":"10.3390\/ijms222011047","article-title":"Role of mitochondria in radiation responses: epigenetic, metabolic, and signaling impacts","volume":"22","author":"Averbeck","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"1","key":"10.1016\/j.radonc.2026.111617_b0210","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1038\/s41598-018-19930-w","article-title":"Mitochondrial biogenesis and metabolic hyperactivation limits the application of MTT assay in the estimation of radiation induced growth inhibition","volume":"8","author":"Rai","year":"2018","journal-title":"Sci Rep"},{"issue":"23","key":"10.1016\/j.radonc.2026.111617_b0215","doi-asserted-by":"crossref","first-page":"11061","DOI":"10.1158\/0008-5472.CAN-05-1083","article-title":"Rapamycin-sensitive pathway regulates mitochondrial membrane potential, autophagy, and survival in irradiated MCF-7 cells","volume":"65","author":"Paglin","year":"2005","journal-title":"Cancer Res"},{"issue":"10","key":"10.1016\/j.radonc.2026.111617_b0220","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1080\/15384101.2021.1912889","article-title":"The emerging relationship between metabolism and DNA repair","volume":"20","author":"Cucchi","year":"2021","journal-title":"Cell Cycle"},{"issue":"10","key":"10.1016\/j.radonc.2026.111617_b0225","doi-asserted-by":"crossref","first-page":"2056","DOI":"10.1016\/j.celrep.2015.11.015","article-title":"CDK1 enhances mitochondrial bioenergetics for radiation-induced DNA repair","volume":"13","author":"Qin","year":"2015","journal-title":"Cell Rep"}],"container-title":["Radiotherapy and Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0167814026004561?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0167814026004561?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T10:57:03Z","timestamp":1783162623000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0167814026004561"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":45,"alternative-id":["S0167814026004561"],"URL":"https:\/\/doi.org\/10.1016\/j.radonc.2026.111617","relation":{},"ISSN":["0167-8140"],"issn-type":[{"value":"0167-8140","type":"print"}],"subject":[],"published":{"date-parts":[[2026,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Mitochondria-targeted OXPHOS inhibition enhances radiotherapy efficacy by disrupting mitochondrial function","name":"articletitle","label":"Article Title"},{"value":"Radiotherapy and Oncology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.radonc.2026.111617","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Author(s). Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"111617"}}