{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T04:56:14Z","timestamp":1791435374331,"version":"4.3.3"},"reference-count":46,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100011851","name":"Kom op tegen Kanker","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011851","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["18B4122N"],"award-info":[{"award-number":["18B4122N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005026","name":"Stichting Tegen Kanker","doi-asserted-by":"publisher","award":["C\/2020\/1463"],"award-info":[{"award-number":["C\/2020\/1463"]}],"id":[{"id":"10.13039\/501100005026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2026,8,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Hypoxia is an important cause of radiotherapy resistance in head and neck cancers. Cancer cells adapt to hypoxic conditions through various molecular alterations, leading to treatment resistance and tumor progression. A deeper understanding of these hypoxia\u2010induced molecular alterations is essential for future development of effective hypoxia targeting and radiosensitizing therapies. In this study, we tracked (post\u2010)hypoxic cells at single\u2010cell level in HPV\u2010negative and HPV\u2010positive HNSCC models using a hypoxia fate mapping system. We found that (post\u2010)hypoxic cells drive regrowth after radiotherapy in 3D conditions and showed an increased resistance to radiation. Transcriptomic analysis showed that post\u2010hypoxic cells are characterized by a gene expression signature mainly defined by checkpoint regulation. Consistent with these findings, radiotherapy resistant post\u2010hypoxic cells showed a reduced number of radiotherapy\u2010induced micronuclei and mitotic spindle aberrations, indicating a mitotic survival advantage. Inhibition of mitotic checkpoint proteins ATR and CHK1\/2 increased the radiosensitivity of post\u2010hypoxic cells. In conclusion, our findings indicate that radiotherapy resistance in HNSCC cells is associated with mitotic survival advantage of post\u2010hypoxic cells, independent of HPV\u2010status.<\/jats:p>","DOI":"10.1002\/ijc.70479","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T17:23:38Z","timestamp":1776101018000},"page":"1042-1055","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Hypoxia Induces a Mitotic Survival Advantage After Radiotherapy in Head and Neck Cancer Cells"],"prefix":"10.1002","volume":"159","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6053-5993","authenticated-orcid":false,"given":"Marilyn","family":"Wegge","sequence":"first","affiliation":[{"name":"Laboratory of Experimental Radiotherapy, Department of Oncology KU Leuven, University of Leuven  Leuven Belgium"},{"name":"Department of Radiation Oncology Leuven Cancer Institute, UZ Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5456-814X","authenticated-orcid":false,"given":"R\u00fcveyda","family":"Dok","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Radiotherapy, Department of Oncology KU Leuven, University of Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludwig J.","family":"Dubois","sequence":"additional","affiliation":[{"name":"The M\u2010Lab, Department of Precision Medicine, GROW\u2010School for Oncology and Reproduction Maastricht University  Maastricht the Netherlands"},{"name":"Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health The University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Nuyts","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Radiotherapy, Department of Oncology KU Leuven, University of Leuven  Leuven Belgium"},{"name":"Department of Radiation Oncology Leuven Cancer Institute, UZ Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,13]]},"reference":[{"key":"e_1_2_12_2_1","first-page":"1462","article-title":"Squamous Cell Carcinoma of the Oral Cavity, Larynx, Oropharynx and Hypopharynx: EHNS\u2010ESMO\u2010ESTRO Clinical Practice Guidelines for Diagnosis, Treatment and Follow\u2010Up","volume":"31","author":"Machiels J. P.","year":"2020","journal-title":"Oral Oncology"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc704"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2008.12.002"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2017.03.024"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2003.11.030"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2019.00004"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.00562"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-021-00539-4"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.12.7878"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-020-00311-0"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12412-1"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24043763"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-021-00615-0"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13153717"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2015.12.004"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102"},{"key":"e_1_2_12_19_1","article-title":"Fast gene set enrichment analysis","author":"Korotkevich G.","year":"2021","journal-title":"bioRxiv"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-51995-2"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14129"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-7"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08460"},{"key":"e_1_2_12_24_1","volume-title":"R: A Language and Environment for Statistical Computing","author":"R Core Team","year":"2025"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0318-2"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-007-9061-3"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-13-0587"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2013.03.013"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semradonc.2021.09.002"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-017-0012-4"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-803309-8.00022-7"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-16-0239"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.9156"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.22125"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2011.09.010"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/1754-9485.12155"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2012.09.015"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2013.06.011"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-8140(97)00220-X"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2009.10.008"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2024.110592"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1080\/21659087.2016.1187803"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201592775"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13215509"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.044768"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/oncsis.2015.50"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9122598"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.70479","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ijc.70479","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.70479","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T07:06:59Z","timestamp":1782112019000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.70479"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,13]]},"references-count":46,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,8,15]]}},"alternative-id":["10.1002\/ijc.70479"],"URL":"https:\/\/doi.org\/10.1002\/ijc.70479","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,13]]},"assertion":[{"value":"2024-08-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}