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Oncolytic virotherapy represents a promising option for bladder cancer and received in 2024 FDA therapy designation for the treatment of non-invasive high-grade bladder cancer (BLCA). For muscle-invasive bladder cancer (MIBC), preclinical studies demonstrated high efficacy of the oncolytic adenovirus XVir-N-31 in urothelial carcinoma (UC). We analyzed the potency of XVir-N-31 virotherapy as a novel treatment option in SCC. Replication of XVir-N-31 has been described to be facilitated by high expression level of Y-Box binding protein 1 (YB-1). Increased\n                    <jats:italic>YB-1<\/jats:italic>\n                    -mRNA expression was detected in basal\/squamous subtype in TCGA BLCA cohort compared to urothelial and luminal BLCA and correlated with patient outcomes. Furthermore, immunohistochemical staining of 89 SCC on a tissue microarray confirmed strong YB-1 expression in squamous BLCA (sq-BLCA).\n                    <jats:italic>In vitro<\/jats:italic>\n                    , XVir-N-31 showed in subtype-specific cell cultures high rates of infection, replication and cell-killing capacity. In a novel\n                    <jats:italic>in ovo<\/jats:italic>\n                    xenograft model, XVir-N-31 impaired growth of xenografts of patient-derived\n                    <jats:italic>ex vivo<\/jats:italic>\n                    cell lines (p-SCC, p-UC) with growth suppression rates of 39\u201349%. We provide preclinical evidence\n                    <jats:italic>ex vivo<\/jats:italic>\n                    and\n                    <jats:italic>in ovo<\/jats:italic>\n                    for high efficacy of XVir-N-31 based oncolytic virotherapy as novel SCC therapy.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-96419-3","type":"journal-article","created":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T07:59:08Z","timestamp":1744963148000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Oncolytic virotherapy provides a potent therapy option for squamous bladder cancer"],"prefix":"10.1038","volume":"15","author":[{"given":"Julia","family":"Pannhausen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Wirtz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Mantwill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per-Sonne","family":"Holm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Schwamborn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danny D.","family":"Jonigk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen E.","family":"Gschwend","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Rose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine T.","family":"Gaisa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"Nawroth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,18]]},"reference":[{"key":"96419_CR1","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1016\/j.eururo.2019.09.006","volume":"77","author":"A Kamoun","year":"2020","unstructured":"Kamoun, A. et al. 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