{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T12:34:27Z","timestamp":1791722067049,"version":"4.3.4"},"reference-count":0,"publisher":"Bioscientifica","issue":"6","content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,6,1]]},"abstract":"<jats:p>\n                    Aggressive pheochromocytomas and paragangliomas (PPGLs) are difficult to treat, and molecular targeting is being increasingly considered, but with variable results. This study investigates established and novel molecular-targeted drugs and chemotherapeutic agents for the treatment of PPGLs in human primary cultures and murine cell line spheroids. In PPGLs from 33 patients, including 7 metastatic PPGLs, we identified germline or somatic driver mutations in 79% of cases, allowing us to assess potential differences in drug responsivity between pseudohypoxia-associated cluster 1-related (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009\u2009= 10) and kinase signaling-associated cluster 2-related (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009\u2009= 14) PPGL primary cultures. Single anti-cancer drugs were either more effective in cluster 1 (cabozantinib, selpercatinib, and 5-FU) or similarly effective in both clusters (everolimus, sunitinib, alpelisib, trametinib, niraparib, entinostat, gemcitabine, AR-A014418, and high-dose zoledronic acid). High-dose estrogen and low-dose zoledronic acid were the only single substances more effective in cluster 2. Neither cluster 1- nor cluster 2-related patient primary cultures responded to HIF-2a inhibitors, temozolomide, dabrafenib, or octreotide. We showed particular efficacy of targeted combination treatments (cabozantinib\/everolimus, alpelisib\/everolimus, alpelisib\/trametinib) in both clusters, with higher efficacy of some targeted combinations in cluster 2 and overall synergistic effects (cabozantinib\/everolimus, alpelisib\/trametinib) or synergistic effects in cluster 2 (alpelisib\/everolimus). Cabozantinib\/everolimus combination therapy, gemcitabine, and high-dose zoledronic acid appear to be promising treatment options with particularly high efficacy in\n                    <jats:italic>SDHB<\/jats:italic>\n                    -mutant and metastatic tumors. In conclusion, only minor differences regarding drug responsivity were found between cluster 1 and cluster 2: some single anti-cancer drugs were more effective in cluster 1 and some targeted combination treatments were more effective in cluster 2.\n                  <\/jats:p>","DOI":"10.1530\/erc-21-0355","type":"journal-article","created":{"date-parts":[[2022,3,25]],"date-time":"2022-03-25T07:52:15Z","timestamp":1648194735000},"page":"285-306","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":32,"title":["Personalized drug testing in human pheochromocytoma\/paraganglioma primary cultures"],"prefix":"10.1530","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7795-1395","authenticated-orcid":true,"given":"Katharina","family":"Wang","sequence":"first","affiliation":[{"name":"1Department of Internal Medicine IV, University Hospital, LMU Klinikum, Ludwig Maximilian University of Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ina","family":"Sch\u00fctze","sequence":"additional","affiliation":[{"name":"2Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich (USZ) and University of Zurich (UZH), Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Gulde","sequence":"additional","affiliation":[{"name":"3Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6932-333X","authenticated-orcid":true,"given":"Nicole","family":"Bechmann","sequence":"additional","affiliation":[{"name":"4Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, Dresden, Germany"},{"name":"5Department of Internal Medicine III, University Hospital Carl Gustav Carus Dresden, Technische Universit\u00e4t Dresden, Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3549-2477","authenticated-orcid":true,"given":"Susan","family":"Richter","sequence":"additional","affiliation":[{"name":"4Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Helm","sequence":"additional","affiliation":[{"name":"5Department of Internal Medicine III, University Hospital Carl Gustav Carus Dresden, Technische Universit\u00e4t Dresden, Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Lauseker","sequence":"additional","affiliation":[{"name":"6Institute for Medical Information Processing, Biometry, and Epidemiology (IBE), Ludwig Maximilian University of Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Maurer","sequence":"additional","affiliation":[{"name":"1Department of Internal Medicine IV, University Hospital, LMU Klinikum, Ludwig Maximilian University of Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"Reul","sequence":"additional","affiliation":[{"name":"2Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich (USZ) and University of Zurich (UZH), Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald","family":"Spoettl","sequence":"additional","affiliation":[{"name":"1Department of Internal Medicine IV, University Hospital, LMU Klinikum, Ludwig Maximilian University of Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Klink","sequence":"additional","affiliation":[{"name":"7Institute for Clinical Genetics, Faculty of Medicine Carl Gustav Carus, Technische Universit\u00e4t Dresden, Dresden, Germany"},{"name":"8National Center of Genetics, Laboratoire National de Sant\u00e9, Dudelange, Luxembourg"},{"name":"9German Cancer Consortium, Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doreen","family":"William","sequence":"additional","affiliation":[{"name":"9German Cancer Consortium, Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Kn\u00f6sel","sequence":"additional","affiliation":[{"name":"10Institute of Pathology, Ludwig Maximilian University of Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliane","family":"Friemel","sequence":"additional","affiliation":[{"name":"11Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5884-739X","authenticated-orcid":true,"given":"Michel","family":"Bihl","sequence":"additional","affiliation":[{"name":"11Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achim","family":"Weber","sequence":"additional","affiliation":[{"name":"11Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Fankhauser","sequence":"additional","affiliation":[{"name":"1Department of Internal Medicine IV, University Hospital, LMU Klinikum, Ludwig Maximilian University of Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Schober","sequence":"additional","affiliation":[{"name":"1Department of Internal Medicine IV, University Hospital, LMU Klinikum, Ludwig Maximilian University of Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Vetter","sequence":"additional","affiliation":[{"name":"12Department of Visceral and Transplantation Surgery, University Hospital, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Broglie D\u00e4ppen","sequence":"additional","affiliation":[{"name":"13Department of Otorhinolaryngology, University Hospital Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4345-696X","authenticated-orcid":true,"given":"Christian G","family":"Ziegler","sequence":"additional","affiliation":[{"name":"5Department of Internal Medicine III, University Hospital Carl Gustav Carus Dresden, Technische Universit\u00e4t Dresden, Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6104-6676","authenticated-orcid":true,"given":"Martin","family":"Ullrich","sequence":"additional","affiliation":[{"name":"14Department of Radiopharmaceutical and Chemical Biology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Pietzsch","sequence":"additional","affiliation":[{"name":"14Department of Radiopharmaceutical and Chemical Biology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany"},{"name":"15Faculty of Chemistry and Food Chemistry, School of Science, Technische Universit\u00e4t Dresden, Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan R","family":"Bornstein","sequence":"additional","affiliation":[{"name":"5Department of Internal Medicine III, University Hospital Carl Gustav Carus Dresden, Technische Universit\u00e4t Dresden, Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Lottspeich","sequence":"additional","affiliation":[{"name":"1Department of Internal Medicine IV, University Hospital, LMU Klinikum, Ludwig Maximilian University of Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7628-3161","authenticated-orcid":true,"given":"Matthias","family":"Kroiss","sequence":"additional","affiliation":[{"name":"1Department of Internal Medicine IV, University Hospital, LMU Klinikum, Ludwig Maximilian University of Munich, Munich, Germany"},{"name":"16Division of Endocrinology and Diabetes, Department of Medicine I, University Hospital W\u00fcrzburg, University of W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Fassnacht","sequence":"additional","affiliation":[{"name":"16Division of Endocrinology and Diabetes, Department of Medicine I, University Hospital W\u00fcrzburg, University of W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7385-5702","authenticated-orcid":true,"given":"Vera Ursula Julia","family":"Wenter","sequence":"additional","affiliation":[{"name":"17Department of Nuclear Medicine, University Hospital, LMU Klinikum, Ludwig Maximilian University of Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Ladurner","sequence":"additional","affiliation":[{"name":"18Department of General-, Visceral-, and Transplant-Surgery, University Hospital, LMU Klinikum, Ludwig Maximilian University of Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constanze","family":"Hantel","sequence":"additional","affiliation":[{"name":"2Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich (USZ) and University of Zurich (UZH), Zurich, Switzerland"},{"name":"5Department of Internal Medicine III, University Hospital Carl Gustav Carus Dresden, Technische Universit\u00e4t Dresden, Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Reincke","sequence":"additional","affiliation":[{"name":"1Department of Internal Medicine IV, University Hospital, LMU Klinikum, Ludwig Maximilian University of Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graeme","family":"Eisenhofer","sequence":"additional","affiliation":[{"name":"4Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, 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