{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T10:20:10Z","timestamp":1783592410472,"version":"3.55.0"},"reference-count":23,"publisher":"Bioscientifica","issue":"7","content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>BCL-2 is an anti-apoptotic protein expressed by aggressive neuroendocrine neoplasms (NENs). We report a case of a patient with a pancreatic neuroendocrine tumor (pNET) who received venetoclax, a BCL-2-targeting drug for the treatment of chronic lymphocytic leukemia. We further characterized BCL2 expression in NENs from a large multi-institutional patient cohort. Clinical data were abstracted from the records of a patient with a pNET. Next-generation sequencing of DNA (592-gene panel or whole exome) and RNA (whole transcriptome) was performed on 636 NENs of pancreatic (P-NENs), small bowel (SB-NENs), colorectal (CR-NENs), and lung (L-NENs) origin by Caris Life Sciences. Comparisons were performed against site-matched non-NEN cancers. BCL2- or MKI67- high and low cohorts were defined based on the top and bottom quartiles of gene expression. The patient with a pNET who received venetoclax had a partial response in the primary tumor that lasted 30 months. CR-, L-, and P-NENs had significantly higher expression of BCL2 compared to non-NEN counterparts. BCL2 expression was significantly higher in MKI67-high tumors among all NEN subtypes. In P-NENs, there was a higher prevalence of RB1 mutations in BCL2-high vs BCL2-low (40 vs 4.9%, P &amp;lt; 0.005). Patients with BCL2-high P-NENs had significantly decreased overall survival (HR 1.94, 95% CI 1.0\u20133.76, P = 0.047). Immune checkpoint gene expression and T cells were enriched in BCL2-high tumors across all subtypes. In summary, we report the first known case of a pancreatic NET with response to venetoclax. BCL2 expression correlated with high MKI67 expression, worse survival, and a highly immune-enriched microenvironment.<\/jats:p>","DOI":"10.1530\/erc-24-0341","type":"journal-article","created":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T10:40:08Z","timestamp":1749811208000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":0,"title":["Targeting anti-apoptosis as a therapeutic strategy in neuroendocrine neoplasms"],"prefix":"10.1530","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5878-9900","authenticated-orcid":true,"given":"Vineeth","family":"Sukrithan","sequence":"first","affiliation":[{"name":"The Ohio State University Comprehensive Cancer Center 1 , , ,","place":["Columbus, Ohio, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uzair","family":"Ahmed","sequence":"additional","affiliation":[{"name":"The Ohio State University Comprehensive Cancer Center 1 , , ,","place":["Columbus, Ohio, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harris","family":"Krause","sequence":"additional","affiliation":[{"name":"Caris Life Sciences 2 , , ,","place":["Irving, Texas, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nishant","family":"Gandhi","sequence":"additional","affiliation":[{"name":"Caris Life Sciences 2 , , ,","place":["Irving, Texas, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Elliott","sequence":"additional","affiliation":[{"name":"Caris Life Sciences 2 , , ,","place":["Irving, Texas, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Hinton","sequence":"additional","affiliation":[{"name":"Caris Life Sciences 2 , , ,","place":["Irving, Texas, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip","family":"Walker","sequence":"additional","affiliation":[{"name":"Caris Life Sciences 2 , , ,","place":["Irving, Texas, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ari","family":"Vanderwalde","sequence":"additional","affiliation":[{"name":"Caris Life Sciences 2 , , ,","place":["Irving, Texas, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Zhou","sequence":"additional","affiliation":[{"name":"The Ohio State University Comprehensive Cancer Center 1 , , ,","place":["Columbus, Ohio, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dipen C","family":"Patel","sequence":"additional","affiliation":[{"name":"The Ohio State University Comprehensive Cancer Center 1 , , ,","place":["Columbus, Ohio, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emil","family":"Lou","sequence":"additional","affiliation":[{"name":"University of Minnesota 3 , , ,","place":["Minneapolis, Minnesota, 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