{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:28:55Z","timestamp":1787016535909,"version":"build-2736575974"},"reference-count":45,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"30","funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["ZIA BC 011899"],"award-info":[{"award-number":["ZIA BC 011899"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["75N91019D00024"],"award-info":[{"award-number":["75N91019D00024"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,7,24]]},"abstract":"<jats:p>\n                    Gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) are a rare subset of cancers with increasing incidence. Due to their slow growth and lack of targetable mutations, the identification of effective treatments remains limited. One reason behind this stagnation is the lack of applicable, accurate study models. One solution is patient tumor organoids (PTOs) that maintain tumor characteristics and can scale for high throughput assays. In this study, PTOs were generated from 35 tumors of pancreatic, small intestinal, and gastric origin, obtained from 17 patients. Important subtypes including hormone functional and\n                    <jats:italic toggle=\"yes\">MEN1<\/jats:italic>\n                    \/\n                    <jats:italic toggle=\"yes\">VHL<\/jats:italic>\n                    mutant GEP-NETs are represented, with each demonstrating growth in culture while maintaining GEP-NET immunohistochemistry and genomic characteristics. Half of G2\/G3 tumors (10 of 20) could be cultured past passage 6, whereas G1 tumors (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u00a0=\u00a015) were capable of growth until passage 4. Therapeutic targeting of the PTOs displayed both tissue-origin and grade-based response to standard of care and investigational therapies while maintaining patient tumor sensitivity and resistance. Last, a successful PTO xenograft model was developed from one PTO line. This study describes GEP-NET organoid development that demonstrates feasibility for expansion, enabling their use for translational investigations.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aea4296","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T17:58:33Z","timestamp":1784915913000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Expanded GEP-NET organoid culture for personalized therapy evaluation"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4099-6642","authenticated-orcid":true,"given":"Steven D.","family":"Forsythe","sequence":"first","affiliation":[{"name":"Neuroendocrine Cancer Therapy Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, 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Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen G.","family":"Andrews","sequence":"additional","affiliation":[{"name":"Neuroendocrine Cancer Therapy Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamala A.","family":"Kenny","sequence":"additional","affiliation":[{"name":"Neuroendocrine Cancer Therapy Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0941-8662","authenticated-orcid":true,"given":"Martha","family":"Quezado","sequence":"additional","affiliation":[{"name":"Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, 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Frederick National Laboratory for Cancer Research, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7529-0557","authenticated-orcid":true,"given":"Jonathan M.","family":"Hernandez","sequence":"additional","affiliation":[{"name":"Surgical Oncology Program, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7348-7804","authenticated-orcid":true,"given":"Naris","family":"Nilubol","sequence":"additional","affiliation":[{"name":"Surgical Oncology Program, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0503-3704","authenticated-orcid":true,"given":"James 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