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In head and neck squamous cell carcinoma (HNSCC), nimorazole, an oxygen mimic, combined with radiotherapy (RT) enabled to improve loco-regional control (LRC) in some patients with hypoxic tumors but it is unknown whether this holds also for radiochemotherapy (RCTx). Here, we investigated the impact of nimorazole combined with RCTx in HNSCC xenografts and explored molecular biomarkers for its targeted use.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Irradiations were performed with 30 fractions in 6\u00a0weeks combined with weekly cisplatin. Nimorazole was applied before each fraction, beginning with the first or after ten fractions. Effect of RCTx with or without addition of nimorazole was quantified as permanent local control after irradiation. For histological evaluation and targeted gene expression analysis, tumors were excised untreated or after ten fractions. Using quantitative image analysis, micromilieu parameters were determined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Nimorazole combined with RCTx significantly improved permanent local control in two tumor models, and showed a potential improvement in two additional models. In these four models, pimonidazole hypoxic volume (pHV) was significantly reduced after ten fractions of RCTx alone. Our results suggest that nimorazole combined with RCTx might improve TCR compared to RCTx alone if hypoxia is decreased during the course of RCTx but further experiments are warranted to verify this association. Differential gene expression analysis revealed 12 genes as potential for RCTx response. When evaluated in patients with HNSCC who were treated with primary RCTx, these genes were predictive for LRC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Nimorazole combined with RCTx improved local tumor control in some but not in all HNSCC xenografts. We identified prognostic biomarkers with the potential for translation to patients with HNSCC.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12967-023-04439-2","type":"journal-article","created":{"date-parts":[[2023,8,26]],"date-time":"2023-08-26T16:02:18Z","timestamp":1693065738000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Prognostic biomarkers for the response to the radiosensitizer nimorazole combined with RCTx: a pre-clinical trial in HNSCC xenografts"],"prefix":"10.1186","volume":"21","author":[{"given":"Lydia","family":"Koi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1303-3335","authenticated-orcid":false,"given":"Verena","family":"Bitto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corina","family":"Weise","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"M\u00f6bius","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annett","family":"Linge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steffen","family":"L\u00f6ck","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ala","family":"Yaromina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Jos\u00e9","family":"Besso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Valentini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel","family":"Pfeifer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens","family":"Overgaard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Zips","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ina","family":"Kurth","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mechthild","family":"Krause","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Baumann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,8,26]]},"reference":[{"key":"4439_CR1","doi-asserted-by":"crossref","first-page":"4066","DOI":"10.1200\/JCO.2007.12.7878","volume":"25","author":"J Overgaard","year":"2007","unstructured":"Overgaard J. 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Int J Radiat Oncol Biol Phys. 1994;29:87\u201393.","journal-title":"Int J Radiat Oncol Biol Phys"}],"container-title":["Journal of Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-023-04439-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12967-023-04439-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-023-04439-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,26]],"date-time":"2024-10-26T22:29:10Z","timestamp":1729981750000},"score":1,"resource":{"primary":{"URL":"https:\/\/translational-medicine.biomedcentral.com\/articles\/10.1186\/s12967-023-04439-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,26]]},"references-count":56,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["4439"],"URL":"https:\/\/doi.org\/10.1186\/s12967-023-04439-2","relation":{},"ISSN":["1479-5876"],"issn-type":[{"value":"1479-5876","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,26]]},"assertion":[{"value":"11 May 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 August 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 August 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The experiment on xenograft models and the animal facility followed the ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines and were approved according to the institutional guidelines and the German animal welfare regulations (approval agency DD24-5131\/207\/34). Data from the retrospective cohort of the DKTK-ROG that received primary RCTx were first published in Linge et al. []. For this patient cohort, ethical approval of clinical and biological data was obtained from the Ethics Committees of all DKTK partner sites.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Michael Baumann, CEO and Scientific Chair of the German Cancer Research Center (DKFZ, Heidelberg) is responsible for collaborations with a large number of companies and institutions worldwide. In this capacity, he has signed contracts for research funding and\/or collaborations, including commercial transfers, with industry and academia on behalf of his institute(s) and staff. He is a member of several supervisory boards, advisory boards and boards of trustees. Michael Baumann confirms that he has no conflict of interest with respect to this paper. In the past 5\u00a0years, Mechthild Krause received funding for her research projects by Merck KGaA (2018\u20132020 for clinical study) and a publicly funded project with the companies Medipan, Attomol GmbH, GA Generic Assays GmbH, Gesellschaft f\u00fcr medizinische und wissenschaftliche genetische Analysen, Lipotype GmbH, and PolyAn GmbH (2019\u20132022). For the present study, Mechthild Krause confirms that none of the above mentioned funding sources were involved.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"576"}}