{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T07:17:00Z","timestamp":1788419820768,"version":"build-2803163510"},"reference-count":35,"publisher":"The Endocrine Society","issue":"10","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Science Foundation of Peking University Cancer Hospital","award":["ZY202411"],"award-info":[{"award-number":["ZY202411"]}]},{"name":"Key Laboratory of Carcinogenesis and Translational Research of Malignant Tumors, Ministry of Education","award":["2025 Open-9"],"award-info":[{"award-number":["2025 Open-9"]}]},{"DOI":"10.13039\/501100005089","name":"Natural Science Foundation of Beijing Municipal","doi-asserted-by":"publisher","award":["7242020"],"award-info":[{"award-number":["7242020"]}],"id":[{"id":"10.13039\/501100005089","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Science Foundation of Peking University Cancer Hospital","award":["BJCH2025GG04"],"award-info":[{"award-number":["BJCH2025GG04"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Colorectal neuroendocrine neoplasms (NEN) are a rare entity lacking effective pharmacologic therapies. We aimed to address the paucity of preclinical models for colorectal NEN that facilitate the exploration of novel therapeutic strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used 3-dimensional culture techniques to establish colorectal NEN organoids. These organoids were subjected to pathological examination and sequence analyses to verify their neuroendocrine nature. Subsequently, the organoids were subcutaneously implanted into mice to create patient-derived organoid xenograft (PDOX) models. In vitro and in vivo experiments were conducted to identify potential antitumor strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We established 3 colorectal NEN organoids, one of which exhibited a BRAF mutation. These organoids closely recapitulated the original tumors in terms of synaptophysin, chromogranin, CD56, somatostatin receptor 2, and Ki-67 expression. DNA- and RNA-sequence analyses confirmed that the organoids preserved the genetic characteristics of their source tumors. In vitro pharmacological assays demonstrated that BRAF inhibitors (IC50: dabrafenib = 3.766\u2005\u03bcM; encorafenib = 5.454\u2005\u03bcM) and MEK inhibitors (IC50: trametinib = 6.602\u2005nM; binimetinib = 0.749\u2005\u03bcM) effectively inhibited the proliferation of organoids harboring the BRAF mutation. The combination of BRAF and MEK inhibitors (IC50: dabrafenib = 0.505\u2005\u03bcM, trametinib = 6.395\u2005nM; encorafenib = 1.467\u2005\u03bcM, binimetinib = 0.210\u2005\u03bcM) exhibited significant enhanced anticancer effects. PDOX experiments revealed that continuous oral administration of dabrafenib and trametinib resulted in a tumor growth inhibition of 66.27%.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Organoids represent reliable preclinical models for drug screening in colorectal NENs, and BRAF mutations may constitute a promising therapeutic target for patients with colorectal NENs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/jendso\/bvag196","type":"journal-article","created":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T11:44:49Z","timestamp":1787399089000},"source":"Crossref","is-referenced-by-count":0,"title":["Colorectal neuroendocrine neoplasm organoids reveal the potential therapeutic value of targeting BRAF mutations"],"prefix":"10.1210","volume":"10","author":[{"given":"Yanan","family":"Chen","sequence":"first","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute , Beijing 100142 ,","place":["China"]},{"name":"Department of Gastroenterology, Nanchong Central Hospital, The Second Clinical Medical College of North Sichuan Medical College , Nanchong 637000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biao","family":"Fan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute , Beijing 100142 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2930-4668","authenticated-orcid":false,"given":"Zhijie","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute , Beijing 100142 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"issue":"6","key":"2026090302565594300_bvag196-B1","first-page":"471","article-title":"Gastroenteropancreatic neuroendocrine tumors","volume":"68","author":"Cives","year":"2018","journal-title":"CA Cancer J Clin"},{"issue":"1","key":"2026090302565594300_bvag196-B2","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1177\/2050640619865113","article-title":"Change in incidence, characteristics and management of colorectal neuroendocrine tumours in The Netherlands in the last decade","volume":"8","author":"Kooyker","year":"2020","journal-title":"United European Gastroenterol J"},{"key":"2026090302565594300_bvag196-B3","doi-asserted-by":"crossref","first-page":"100510","DOI":"10.1016\/j.lanepe.2022.100510","article-title":"Incidence and survival of neuroendocrine neoplasia in England 1995-2018: a retrospective, population-based study","volume":"23","author":"White","year":"2022","journal-title":"Lancet Reg Health Eur"},{"issue":"3","key":"2026090302565594300_bvag196-B4","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1097\/DCR.0000000000000298","article-title":"Survival of patients with neuroendocrine carcinoma of the colon and rectum: a population-based analysis","volume":"58","author":"Shafqat","year":"2015","journal-title":"Dis Colon Rectum. 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