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Human papilloma virus (HPV)-positive ones are induced by virus infection and generally have a good prognosis due to their chemo- and radiosensitivity. In contrast, HPV-negative HNSCCs are primarily caused by tobacco and alcohol abuse; patients have a poor prognosis resulting in the need of innovative targeted and combinatory treatment options. Therefore, we combined the Mre11-Rad50-Nbs1 (MRN) inhibitor Mirin with ionizing radiation (IR). Our hypothesis is that the inhibition of the cancer cells\u2019 DNA damage response (DDR) by Mirin leads to reduced repair capacity and a radiosensitization of the cancer cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We investigated the effect of Mirin in combination with IR on five HPV-negative and two HPV-positive HNSCC cell lines and one primary fibroblast cell line - serving as healthy control - in several functional assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We suggest \u2013 on the one hand - that Mirin shows a trend towards radiosensitizing effects regarding cell death, cell cycle distribution, colony formation, and deoxyribonucleic acid (DNA) damage in HPV-negative HNSCC cell lines but not in HPV-positive ones. On the other hand, the healthy control was nearly unaffected by the combinatory treatment which indicates low side effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>It is useful to generate a deeper insight into the underlying cellular mechanisms of Mirin response in future studies and further validate Mirin\u2019s potential radiosensitizing effect in HPV-negative HNSCCs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12935-026-04218-1","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T09:33:55Z","timestamp":1770197635000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The inhibition of the MRN complex by Mirin radiosensitizes particularly HPV-negative HNSCC cell lines"],"prefix":"10.1186","volume":"26","author":[{"given":"Laura S.","family":"Hildebrand","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Babak Pornour","family":"Mehravani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Khalifa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Schiller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janis","family":"Langkr\u00e4r","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Jost","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rainer","family":"Fietkau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luitpold V.","family":"Distel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,4]]},"reference":[{"issue":"1","key":"4218_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2024.189230","volume":"1880","author":"Y Wang","year":"2025","unstructured":"Wang Y, Han J, Zhu Y, Huang N, Qu N. 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