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Wang, K.* ; Schober, L.* ; Fischer, A.* ; Bechmann, N.* ; Maurer, J.* ; Peischer, L.* ; Reul, A.* ; Hantel, C.* ; Reincke, M.* ; Beuschlein, F.* ; Robledo, M.* ; Mohr, H. ; Pellegata, N.S. ; Schilbach, K.* ; Knösel, T.* ; Ilmer, M.* ; Angele, M.* ; Kroiss, M.* ; Maccio, U.* ; Broglie-Däppen, M.* ; Vetter, D.* ; Lehmann, K.* ; Pacak, K.* ; Grossman, A.B.* ; Auernhammer, C.J.* ; Zitzmann, K.* ; Nölting, S.*

Opposing effects of cannabidiol in patient-derived neuroendocrine tumor, pheochromocytoma/paraganglioma primary cultures.

J. Clin. Endocrinol. Metab., DOI: 10.1210/clinem/dgae241 (2024)
Postprint DOI PMC
CONTEXT: Treatment options for advanced neuroendocrine tumors (NETs), pheochromocytomas and paragangliomas (together PPGLs) are still limited. In recent years, anti-tumor effects of cannabinoids have been reported; however, there are only very limited data available in NETs or PPGLs. OBJECTIVE: Investigation of the effects of cannabidiol (CBD) on patient-derived human NET/PPGL primary cultures and on NET/PPGL cell lines. METHODS: We established primary cultures derived from 46 different patients with PPGLs (n = 35) or NETs (n = 11) who underwent tumor resection at two centers. Treatment of patient primary cultures with clinically relevant doses (5 µM) and slightly higher doses (10 µM) of CBD was performed. RESULTS: We found opposing effects of 5 µM CBD: significant anti-tumor effects in 5/35 (14%) and significant tumor-promoting effects in 6/35 (17%) of PPGL primary cultures. In terms of anti-tumor effects, cluster 2-related PPGLs showed significantly stronger responsivity to CBD compared to cluster 1-related PPGLs (p = 0.042). Of the cluster 2-related tumors, NF1 PPGLs showed strongest responsivity (4/5 PPGL primary cultures with a significant decrease in cell viability were NF1-mutated). We also found opposing effects of 10 µM CBD in PPGLs and NETs: significant anti-tumor effects in 9/33 of PPGL (27%) and 3/11 of NET (27%) primary cultures, significant tumor-promoting effects in 6/33 of PPGL (18%) and 2/11 of NET (18%) primary cultures. CONCLUSIONS: We suggest a potential novel treatment option for some NETs/PPGLs, but also provide evidence for caution when applying cannabinoids as supportive therapy for pain or appetite management to cancer patients, and possibly as health supplements.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Cbd ; Cannabidiol ; Cannabinoids ; Neuroendocrine Tumor ; Pheochromocytoma And Paraganglioma; Cancer-related Pain; Medical Cannabis; Landscape; Neoplasms; Paraganglioma; Everolimus; Management; Therapy; Update; Cells
Language english
Publication Year 2024
HGF-reported in Year 2024
ISSN (print) / ISBN 0021-972X
e-ISSN 1945-7197
Journal Journal of Clinical Endocrinology & Metabolism, The
Publisher Endocrine Society
Publishing Place Bethesda, Md.
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Cancer (IDC)
POF-Topic(s) 30201 - Metabolic Health
Research field(s) Helmholtz Diabetes Center
PSP Element(s) G-502590-001
Grants Immuno-TargET project under the umbrella of University Medicine Zurich
German Research Foundation
DOI 10.1210/clinem/dgae241
WOS ID 001214258100001
PubMed ID 38605427
Erfassungsdatum 2024-06-05
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