{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T13:19:05Z","timestamp":1780406345912,"version":"3.54.1"},"reference-count":44,"publisher":"The Endocrine Society","issue":"6","license":[{"start":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T00:00:00Z","timestamp":1768003200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003383","name":"CRC","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003383","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008672","name":"Wilhelm Sander-Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008672","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Precision medicine has transformed many areas in oncology. However, it remains largely unexplored in metastatic gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs), where there is a need for further innovative therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate individual tumor responses to different agents, we have established a standardized personalized drug screening and risk assessment platform using patient-derived GEP-NEN primary cultures (n = 23, 16\/23 from metastatic tumors, n = 12 small intestinal neuroendocrine tumors [siNETs], n = 10 pancreatic NETs [pNETs], n = 1 neuroendocrine carcinoma [NEC]).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We assessed GEP-NEN primary culture cell viability, performed signaling pathway analysis by automated Western blotting and immunohistochemically evaluated tumor composition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Systematic drug testing of 27 agents including signaling inhibitors (i) (mechanistic target of rapamycin inhibitor [mTORi] everolimus, tyrosine kinase inhibitors cabozantinib\/sunitinib, AKTi capivasertib, PI3Ki alpelisib, CDK4\/6i ribociclib), DNA damage response inhibitors (PARPi niraparib, WEE1i adavosertib, ATRi berzosertib), chemotherapeutics (temozolomide, 5-fluorouracil, lurbinectedin), drug repurposed agents (zoledronic acid), and a personalized risk assessment (glucagon-like peptide [GLP]-2 analogue teduglutide, GLP-1 analogue semaglutide, sex hormones) was performed. We demonstrated statistically significant group effects and individualized responsiveness\/resistance data. We identified differences in drug response between pNETs\/siNETs and between GEP-NETs\/GEP-NEC, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We provide novel data on the efficacy of putative and established therapies in patient-derived GEP-NEN primary cultures. Our standardized platform for personalized drug screening and risk assessment in GEP-NEN primary cultures enables prediction of individual tumor treatment response in this orphan disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgaf705","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T12:48:07Z","timestamp":1767962887000},"page":"1539-1553","source":"Crossref","is-referenced-by-count":1,"title":["Personalized Drug Screening and Risk Assessment in Patient-Derived Gastroenteropancreatic Neuroendocrine Neoplasms"],"prefix":"10.1210","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8087-3722","authenticated-orcid":false,"given":"Christoph J","family":"Auernhammer","sequence":"first","affiliation":[{"name":"Department of Medicine IV, LMU University Hospital, LMU Munich , 80336 Munich ,","place":["Germany"]},{"name":"Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM, ENETS Centre of Excellence), LMU University Hospital , 81377 Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7795-1395","authenticated-orcid":false,"given":"Katharina","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicine IV, LMU University Hospital, LMU Munich , 80336 Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umberto","family":"Maccio","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Pathology, University Hospital Zurich , Zurich CH-8091 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Kn\u00f6sel","sequence":"additional","affiliation":[{"name":"Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM, ENETS Centre of Excellence), LMU University Hospital , 81377 Munich ,","place":["Germany"]},{"name":"Institute of Pathology, Faculty of Medicine, LMU Munich , 80337 Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian P","family":"Hungbauer","sequence":"additional","affiliation":[{"name":"Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM, ENETS Centre of Excellence), LMU University Hospital , 81377 Munich ,","place":["Germany"]},{"name":"Department of General, Visceral and Transplantation Surgery, LMU University Hospital , 81377 Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8667-0296","authenticated-orcid":false,"given":"Katharina","family":"Schilbach","sequence":"additional","affiliation":[{"name":"Department of Medicine IV, LMU University Hospital, LMU Munich , 80336 Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Maurer","sequence":"additional","affiliation":[{"name":"Department of Medicine IV, LMU University Hospital, LMU Munich , 80336 Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea","family":"Peischer","sequence":"additional","affiliation":[{"name":"Department of Medicine IV, LMU University Hospital, LMU Munich , 80336 Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"Reul","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich , Zurich CH-8091 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Kuzmenko","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich , Zurich CH-8091 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edlira","family":"Luca","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich , Zurich CH-8091 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Hamati","sequence":"additional","affiliation":[{"name":"Department of Medicine IV, LMU University Hospital, LMU Munich , 80336 Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Vetter","sequence":"additional","affiliation":[{"name":"Department of Visceral and Transplantation Surgery, University Hospital Zurich , Zurich CH-8091 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Oberholzer","sequence":"additional","affiliation":[{"name":"Department of Visceral and Transplantation Surgery, University Hospital Zurich , Zurich CH-8091 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9639-3213","authenticated-orcid":false,"given":"Ralph","family":"Fritsch","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Hematology, University Hospital Zurich , Zurich CH-8091 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karel","family":"Pacak","sequence":"additional","affiliation":[{"name":"Center for Adrenal Endocrine Tumors, AKESO , Prague 5 ,","place":["Czech Republic"]},{"name":"Faculty of Medicine, Palacky University , 779 00 Olomouc ,","place":["Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley B","family":"Grossman","sequence":"additional","affiliation":[{"name":"Green Templeton College, University of Oxford , Oxford OX2 6HG ,","place":["UK"]},{"name":"NET Unit, ENETS 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IV, LMU University Hospital, LMU Munich , 80336 Munich ,","place":["Germany"]},{"name":"Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM, ENETS Centre of Excellence), LMU University Hospital , 81377 Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8906-2563","authenticated-orcid":false,"given":"Constanze","family":"Hantel","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich , Zurich CH-8091 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2341-3161","authenticated-orcid":false,"given":"Kathrin","family":"Zitzmann","sequence":"additional","affiliation":[{"name":"Department of Medicine IV, LMU University Hospital, LMU Munich , 80336 Munich 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