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The tumoroids recapitulate genomic and transcriptomic characteristics of the corresponding patient tumors and capture intrapatient tumor heterogeneity. Organoid drug profiling using a library of 153 clinical compounds identified methotrexate as an effective and selective drug against SCCOHTs with a clinically relevant IC\n            <jats:sub>50<\/jats:sub>\n            of 35 nanomolars. RNA sequencing demonstrated that methotrexate induced TP53 pathway activation and apoptosis. These data underscore that organoid technology can support the design of therapeutic strategies for rare cancers.\n          <\/jats:p>","DOI":"10.1126\/sciadv.adq1724","type":"journal-article","created":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T18:58:46Z","timestamp":1740596326000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":15,"title":["Organoid drug profiling identifies methotrexate as a therapy for SCCOHT, a rare pediatric cancer"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8566-839X","authenticated-orcid":true,"given":"Seok-Young","family":"Kim","sequence":"first","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, Netherlands."},{"name":"Oncode Institute, Utrecht, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5976-023X","authenticated-orcid":true,"given":"Tamar A. 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