{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T18:22:53Z","timestamp":1792174973299,"version":"4.4.0"},"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":"\n Therapies for metastatic\n SDHB<\/jats:italic>\n -dependent pheochromocytoma and paraganglioma (PPGL) are limited and poorly efficient. New targeted therapies and identification of early non-invasive biomarkers of response are thus urgently needed for these patients. We characterized an\n in vivo<\/jats:italic>\n allograft model of spontaneously immortalized murine chromaffin cells (imCC) with inactivation of the\n Sdhb<\/jats:italic>\n gene by dynamic contrast-enhanced MRI (DCE-MRI) and\n 18<\/jats:sup>\n FDG-PET. We evaluated the response to several therapies: IACS-010759 (mitochondrial respiratory chain complex I inhibitor), sunitinib (tyrosine kinase inhibitor with anti-angiogenic activity), talazoparib (poly ADP ribose polymerase (PARP) inhibitor) combined or not to temozolomide (alkylating agent), pharmacological inhibitors of HIF2a (PT2385 and PT2977 (belzutifan)) and molecular inactivation of HIF2a (imCC\n \n Sdhb\n \u2212\/\u2212<\/jats:sup>\n <\/jats:italic>\n shHIF2a). Multimodal imaging was performed, including magnetic resonance spectroscopy (\n 1<\/jats:sup>\n H-MRS) to monitor the level of succinate\n in vivo<\/jats:italic>\n . The allografted model of\n \n Sdhb\n \u2212\/\u2212<\/jats:sup>\n <\/jats:italic>\n imCC reflected SDHB-deficient tumors, with increased angiogenesis and a particular avidity for\n 18<\/jats:sup>\n FDG. After 14 days of treatment, IACS-010759, sunitinib and talazoparib at high doses allowed a significant reduction of the tumor volumes. In contrast to the tumor growth inhibition observed in\n \n Sdhb\n \u2212\/\u2212<\/jats:sup>\n <\/jats:italic>\n shHIF2a imCC tumors, pharmacological inhibitors of HIF2a (PT2385 and belzutifan) showed no antitumor action in this model, alone or in combination with sunitinib.\n 1<\/jats:sup>\n H-MRS, but not DCE-MRI, enabled the monitoring response to sunitinib, which was the best treatment in this study, promoting a decrease in succinate levels detected\n in vivo<\/jats:italic>\n . This study paves the way for new therapeutic options and reveals a potential new early biomarker of response to treatment in\n SDHB<\/jats:italic>\n -dependent PPGL.\n <\/jats:p>","DOI":"10.1530\/erc-22-0030","type":"journal-article","created":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T10:20:36Z","timestamp":1648549236000},"page":"375-388","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":11,"title":["Preclinical evaluation of targeted therapies in Sdhb-mutated tumors"],"prefix":"10.1530","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9920-0480","authenticated-orcid":true,"given":"Sophie","family":"Moog","sequence":"first","affiliation":[{"name":"1Universit\u00e9 de Paris Cit\u00e9, PARCC INSERM UMR970, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0889-0226","authenticated-orcid":true,"given":"Betty","family":"Salgues","sequence":"additional","affiliation":[{"name":"2PARCC INSERM UMR970, Paris, France"},{"name":"6Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Europ\u00e9en Georges Pompidou, Service de Radiologie, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmine","family":"Braik-Djellas","sequence":"additional","affiliation":[{"name":"1Universit\u00e9 de Paris Cit\u00e9, PARCC INSERM UMR970, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Viel","sequence":"additional","affiliation":[{"name":"1Universit\u00e9 de Paris Cit\u00e9, PARCC INSERM UMR970, Paris, France"},{"name":"3Sorbonne Universit\u00e9, Service de M\u00e9decine Nucl\u00e9aire, Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Piti\u00e9 Salp\u00eatri\u00e8re, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Balvay","sequence":"additional","affiliation":[{"name":"1Universit\u00e9 de Paris Cit\u00e9, PARCC INSERM UMR970, Paris, France"},{"name":"3Sorbonne Universit\u00e9, Service de M\u00e9decine Nucl\u00e9aire, Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Piti\u00e9 Salp\u00eatri\u00e8re, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwennhael","family":"Autret","sequence":"additional","affiliation":[{"name":"1Universit\u00e9 de Paris Cit\u00e9, PARCC INSERM UMR970, Paris, France"},{"name":"3Sorbonne Universit\u00e9, Service de M\u00e9decine Nucl\u00e9aire, Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Piti\u00e9 Salp\u00eatri\u00e8re, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estelle","family":"Robidel","sequence":"additional","affiliation":[{"name":"1Universit\u00e9 de Paris Cit\u00e9, PARCC INSERM UMR970, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Paule","family":"Gimenez-Roqueplo","sequence":"additional","affiliation":[{"name":"1Universit\u00e9 de Paris Cit\u00e9, PARCC INSERM UMR970, Paris, France"},{"name":"4Plateforme d\u2019Imageries du Vivant, Universit\u00e9 de Paris Cit\u00e9, Facult\u00e9 de M\u00e9decine, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5349-8194","authenticated-orcid":true,"given":"Bertrand","family":"Tavitian","sequence":"additional","affiliation":[{"name":"1Universit\u00e9 de Paris Cit\u00e9, PARCC INSERM UMR970, Paris, France"},{"name":"3Sorbonne Universit\u00e9, Service de M\u00e9decine Nucl\u00e9aire, Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Piti\u00e9 Salp\u00eatri\u00e8re, Paris, France"},{"name":"5Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Europ\u00e9en Georges Pompidou, Service de G\u00e9n\u00e9tique, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Lussey-Lepoutre","sequence":"additional","affiliation":[{"name":"2PARCC INSERM UMR970, Paris, France"},{"name":"6Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Europ\u00e9en Georges Pompidou, Service de Radiologie, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8190-5853","authenticated-orcid":true,"given":"Judith","family":"Favier","sequence":"additional","affiliation":[{"name":"1Universit\u00e9 de Paris Cit\u00e9, PARCC INSERM UMR970, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","container-title":["Endocrine-Related Cancer"],"original-title":[],"link":[{"URL":"https:\/\/erc.bioscientifica.com\/view\/journals\/erc\/29\/6\/ERC-22-0030.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/erc.bioscientifica.com\/downloadpdf\/journals\/erc\/29\/6\/ERC-22-0030.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:56:14Z","timestamp":1784555774000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/erc\/article\/29\/6\/375-388\/25632"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,1]]},"references-count":0,"journal-issue":{"issue":"6"},"URL":"https:\/\/doi.org\/10.1530\/erc-22-0030","relation":{},"ISSN":["1351-0088","1479-6821"],"issn-type":[{"value":"1351-0088","type":"print"},{"value":"1479-6821","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,1]]}}}