{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T01:02:39Z","timestamp":1790298159163,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Neuroendocrinology"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Clinically non\u2010functioning pituitary neuroendocrine tumors (NF\u2010PitNETs) lack effective medical therapies, and the role of somatostatin receptor ligands (SRLs) and dopamine agonists (DAs) in this setting is controversial. We evaluated the in vitro response of NF\u2010PitNETs to multiple SRL and\/or DA treatments, focusing on the role of receptor expression and tumor characteristics in driving tumor response. Forty\u2010four NF\u2010PitNET primary cultures were treated (72\u2009h, 10\u2009nM) with octreotide (OCT), pasireotide (PAS), OCT\u2009+\u2009PAS, BIM\u201053097 (D2R agonist), BIM\u201053097\u2009+\u2009PAS, and BIM\u201023B065 (SSTR2\/SSTR5\/D2R preferential ligand) to evaluate cell proliferation inhibition. Tumors were considered responders to a treatment when a \u226520% reduction in cell proliferation was observed (vs. control); responder tumors to at least one tested condition were classified into the \u201cresponder group\u201d for further analysis. Somatostatin (SSTRs) and dopamine type 2 receptor (D2R) expression were evaluated through immunohistochemistry. Data on radiological invasiveness, proliferation indices (Ki67%, mitoses), and p53 immunostaining were collected. Tumor grade was determined using Trouillas and PANOMEN\u20103 classifications. Median patient age at surgery was 60.3\u2009years (IQR 49.7\u201370.7), 29 were males (71%). Overall, no significant in vitro inhibition of cell proliferation was observed [ranging from \u22124.2% (OCT and PAS) to \u22127.4% (BIM\u201053097\u2009+\u2009PAS)]. However, 13 cultures (30%) were included in the \u201cresponder group\u201d [mean inhibition ranging from \u221218.6% (OCT) to \u221227.7% (BIM\u201053097\u2009+\u2009PAS)]. D2R was the most expressed receptor (median IRS 8, IQR 6\u20138), followed by SSTR1 and SSTR2 (median IRS 4, IQR 3\u20136); SSTR3 and SSTR5 expression was low. In the whole cohort, OCT and PAS efficacy directly correlated with SSTR2 (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u2009.013 and\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u2009.027, respectively). D2R and SSTR2 expression was higher in responders vs. non\u2010responders to BIM\u201023B065 (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u2009.017 and\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u2009.042, respectively). ROC curve analysis discriminates BIM\u201023B065 responders based on D2R and SSTR2 expression with acceptable ability (AUC\u2009=\u20090.784 and AUC\u2009=\u20090.743, respectively). However, the \u201cresponder group\u201d did not differ significantly from the \u201cnon\u2010responder group\u201d with respect to patient demographics, tumor clinical\u2013pathological characteristics, receptor expression, and grading. In conclusion, we confirm the limited efficacy of SRL and DA treatment in NF\u2010PitNETs. D2R and SSTR2 can discriminate tumors responsive to BIM\u201023B065. As concerns the other tested compounds, none of the tumor parameters evaluated demonstrated robust predictive value for NF\u2010PitNET in vitro response.\n                  <\/jats:p>","DOI":"10.1111\/jne.70272","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:41:50Z","timestamp":1790296910000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Predictors of in vitro response to somatostatin and dopamine receptor\u2010targeted treatments are lacking in clinically non\u2010functioning pituitary tumors"],"prefix":"10.1111","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4974-2075","authenticated-orcid":false,"given":"Claudia","family":"Campana","sequence":"first","affiliation":[{"name":"Endocrinology Unit, Department of Internal Medicine and Medical Specialties (DIMI), School of Medical and Pharmaceutical Sciences University of Genova  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6190-3017","authenticated-orcid":false,"given":"Jessica","family":"Amar\u00f9","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Internal Medicine and Medical Specialties (DIMI), School of Medical and Pharmaceutical Sciences University of Genova  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4166-0139","authenticated-orcid":false,"given":"Diego Criminelli","family":"Rossi","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery IRCCS AOM \u2013 Policlinico San Martino  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6059-3982","authenticated-orcid":false,"given":"Anna","family":"Arecco","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Internal Medicine and Medical Specialties (DIMI), School of Medical and Pharmaceutical Sciences University of Genova  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Nozza","sequence":"additional","affiliation":[{"name":"Pathology Unit IRCCS AOM \u2013 Policlinico San Martino  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9383-0913","authenticated-orcid":false,"given":"Mara","family":"Boschetti","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Internal Medicine and Medical Specialties (DIMI), School of Medical and Pharmaceutical Sciences University of Genova  Genoa Italy"},{"name":"Endocrinology Unit IRCCS AOM \u2013 Policlinico San Martino  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3577-7894","authenticated-orcid":false,"given":"Gianluigi","family":"Zona","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery IRCCS AOM \u2013 Policlinico San Martino  Genoa Italy"},{"name":"Neurosurgery Unit, Department of Neuroscience, Ophthalmology, Genetics and Childhood and Maternal sciences (DiNOGMI) University of Genova  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1410-6143","authenticated-orcid":false,"given":"Diego","family":"Ferone","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Internal Medicine and Medical Specialties (DIMI), School of Medical and Pharmaceutical Sciences University of Genova  Genoa Italy"},{"name":"Endocrinology Unit IRCCS AOM \u2013 Policlinico San Martino  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9504-7578","authenticated-orcid":false,"given":"Marica","family":"Arvigo","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Internal Medicine and Medical Specialties (DIMI), School of Medical and Pharmaceutical Sciences University of Genova  Genoa Italy"},{"name":"Endocrinology Unit IRCCS AOM \u2013 Policlinico San Martino  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5062-9208","authenticated-orcid":false,"given":"Federico","family":"Gatto","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Internal Medicine and Medical Specialties (DIMI), School of Medical and Pharmaceutical Sciences University of Genova  Genoa Italy"},{"name":"Endocrinology Unit IRCCS AOM \u2013 Policlinico San Martino  Genoa 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