{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:06:17Z","timestamp":1790762777628,"version":"4.1.0"},"reference-count":13,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>High\u2010risk neuroblastoma remains a leading cause of pediatric cancer mortality, and improved preclinical models are needed to guide therapeutic developments. We screened seven high\u2010risk neuroblastoma cell lines and three patient\u2010derived tumor organoids with 528 compounds alongside bone marrow controls, and compared them with external datasets. Unsupervised clustering of drug response clearly separated two\u2010dimensional (2D) and three\u2010dimensional (3D) models, with 3D models showing more coherent responses and overall higher drug sensitivity. Mitotic and DNA\u2010damage pathways emerged as key vulnerabilities, and standard\u2010of\u2010care compounds, including doxorubicin, etoposide, and topotecan, were more active in 3D than 2D. This work highlights the potential of 3Dmodels as useful tools for therapy prioritization in neuroblastoma.<\/jats:p>","DOI":"10.1002\/1545-5017.70696","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:53:28Z","timestamp":1790762008000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative Drug Response Profiling in Neuroblastoma Cell Lines and Patient\u2010Derived Tumor Organoids"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6896-7846","authenticated-orcid":false,"given":"Krzysztof","family":"Wierbi\u0142owicz","sequence":"first","affiliation":[{"name":"Department of Oncology\u2010Pathology Karolinska Institutet Science for Life Laboratory  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1261-7505","authenticated-orcid":false,"given":"Se Whee Sammy","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Oncology\u2010Pathology Karolinska Institutet Science for Life Laboratory  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aironas","family":"Los","sequence":"additional","affiliation":[{"name":"Department of Oncology\u2010Pathology Karolinska Institutet Science for Life Laboratory  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5968-4324","authenticated-orcid":false,"given":"Ernest","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Oncology\u2010Pathology Karolinska Institutet Science for Life Laboratory  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6975-0753","authenticated-orcid":false,"given":"Nona","family":"Struyf","sequence":"additional","affiliation":[{"name":"Department of Oncology\u2010Pathology Karolinska Institutet Science for Life Laboratory  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Erkers","sequence":"additional","affiliation":[{"name":"Department of Oncology\u2010Pathology Karolinska Institutet Science for Life Laboratory  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8374-8978","authenticated-orcid":false,"given":"S\u00f6ren","family":"Lehmann","sequence":"additional","affiliation":[{"name":"Department of Medicine Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan J.","family":"Molenaar","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology  Utrecht The Netherlands"},{"name":"Department of Pharmaceutical Sciences Utrecht University  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob","family":"Stenman","sequence":"additional","affiliation":[{"name":"Department of Women's and Children's Health Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olli","family":"Kallioniemi","sequence":"additional","affiliation":[{"name":"Department of Oncology\u2010Pathology Karolinska Institutet Science for Life Laboratory  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5501-466X","authenticated-orcid":false,"given":"P\u00e4ivi","family":"\u00d6stling","sequence":"additional","affiliation":[{"name":"Department of Oncology\u2010Pathology Karolinska Institutet Science for Life Laboratory  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8658-5967","authenticated-orcid":false,"given":"Brinton","family":"Seashore\u2010Ludlow","sequence":"additional","affiliation":[{"name":"Department of Oncology\u2010Pathology Karolinska Institutet Science for Life Laboratory  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0162-1354","authenticated-orcid":false,"given":"Kasper","family":"Karlsson","sequence":"additional","affiliation":[{"name":"Department of Oncology\u2010Pathology Karolinska Institutet Science for Life Laboratory  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"issue":"23","key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"2202","DOI":"10.1056\/NEJMra0804577","article-title":"Recent Advances in Neuroblastoma","volume":"362","author":"Maris J. M.","year":"2010","journal-title":"New England Journal of Medicine"},{"key":"e_1_2_10_3_1","doi-asserted-by":"crossref","DOI":"10.1038\/nrdp.2016.78","article-title":"Neuroblastoma","volume":"2","author":"Matthay K. K.","year":"2016","journal-title":"Nature Reviews Disease Primers"},{"issue":"14","key":"e_1_2_10_4_1","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1056\/NEJMoa0911123","article-title":"Anti\u2010GD2 Antibody With GM\u2010CSF, Interleukin\u20102, and Isotretinoin for Neuroblastoma","volume":"363","author":"Yu A. L.","year":"2010","journal-title":"New England Journal of Medicine"},{"issue":"4","key":"e_1_2_10_5_1","first-page":"266","article-title":"Modeling Physiological Events in 2D vs. 3D Cell Culture","volume":"32","author":"Duval K.","year":"2017","journal-title":"Physiology (Bethesda)"},{"issue":"4","key":"e_1_2_10_6_1","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1089\/adt.2014.573","article-title":"Three\u2010Dimensional Cell Culture Systems and Their Applications in Drug Discovery and Cell\u2010Based Biosensors","volume":"12","author":"Edmondson R.","year":"2014","journal-title":"Assay and Drug Development Technologies"},{"issue":"1","key":"e_1_2_10_7_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.jbiotec.2010.01.012","article-title":"Multicellular Tumor Spheroids: An Underestimated Tool Is Catching up Again","volume":"148","author":"Hirschhaeuser F.","year":"2010","journal-title":"Journal of Biotechnology"},{"issue":"1","key":"e_1_2_10_8_1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.stem.2019.10.010","article-title":"Patient\u2010Derived Organoids Predict Chemoradiation Responses of Locally Advanced Rectal Cancer","volume":"26","author":"Yao Y.","year":"2020","journal-title":"Cell Stem Cell"},{"issue":"3","key":"e_1_2_10_9_1","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1016\/j.ejca.2013.11.015","article-title":"Newly\u2010Derived Neuroblastoma Cell Lines Propagated in Serum\u2010Free Media Recapitulate the Genotype and Phenotype of Primary Neuroblastoma Tumours","volume":"50","author":"Bate\u2010Eya L. T.","year":"2014","journal-title":"European Journal of Cancer"},{"key":"e_1_2_10_10_1","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2022.1085270","article-title":"Patient\u2010Derived Models: Advanced Tools for Precision Medicine in Neuroblastoma","volume":"12","author":"Aaltonen K.","year":"2022","journal-title":"Frontiers in Oncology"},{"key":"e_1_2_10_11_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejca.2025.115275","article-title":"Exploring High\u2010Throughput Drug Sensitivity Testing in Neuroblastoma Cell Lines and Patient\u2010Derived Tumor Organoids in the Era of Precision Medicine","volume":"218","author":"Langenberg K. P. 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