{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T19:14:53Z","timestamp":1792696493766,"version":"4.5.0"},"reference-count":0,"publisher":"Bioscientifica","issue":"8","content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:p>\n                    Pheochromocytomas and paragangliomas (PPGLs) are adrenal or extra-adrenal autonomous nervous system-derived tumors. Most PPGLs are benign, but approximately 15% progress with metastases (mPPGLs). mPPGLs are more likely to occur in patients with large pheochromocytomas, sympathetic paragangliomas, and norepinephrine-secreting tumors. Older subjects, those with larger tumors and synchronous metastases, advance more rapidly. Germline mutations of\n                    <jats:italic>SDHB<\/jats:italic>\n                    ,\n                    <jats:italic>FH<\/jats:italic>\n                    , and possibly\n                    <jats:italic>SLC25A11<\/jats:italic>\n                    , or somatic\n                    <jats:italic>MAML3<\/jats:italic>\n                    disruptions relate to a higher risk for metastatic disease. However, it is unclear whether these mutations predict outcome. Once diagnosed, there are no well-established predictors of outcome in mPPGLs, and aggressive tumors have few therapeutic options and limited response. High-specific activity (HSA) metaiodine-benzyl-guanidine (MIBG) is the first FDA approved treatment and shows clinical effectiveness for MIBG-avid mPPGLs. Ongoing and future investigations should involve validation of emerging candidate outcome biomarkers, including somatic\n                    <jats:italic>ATRX<\/jats:italic>\n                    ,\n                    <jats:italic>TERT<\/jats:italic>\n                    , and microRNA disruptions and identification of novel prognostic indicators. Long-term effect of HSA-MIBG and the role of other radiopharmaceuticals should be investigated. Novel trials targeting molecular events prevalent in\n                    <jats:italic>SDHB<\/jats:italic>\n                    \/\n                    <jats:italic>FH<\/jats:italic>\n                    mutant tumors, such as activated hypoxia inducible factor 2 (HIF2), angiogenesis, or other mitochondrial defects that might confer unique vulnerability to these tumors should be developed and initiated. As therapeutic options are anticipated to expand, multi-institutional collaborations and well-defined clinical and molecular endpoints will be critical to achieve higher success rates in improving care for patients with mPPGLs.\n                  <\/jats:p>","DOI":"10.1530\/erc-19-0435","type":"journal-article","created":{"date-parts":[[2020,2,18]],"date-time":"2020-02-18T12:16:05Z","timestamp":1582028165000},"page":"T41-T52","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":46,"title":["HEREDITARY ENDOCRINE TUMOURS: CURRENT STATE-OF-THE-ART AND RESEARCH OPPORTUNITIES: Metastatic pheochromocytomas and paragangliomas: proceedings of the MEN2019 workshop"],"prefix":"10.1530","volume":"27","author":[{"given":"Patricia L M","family":"Dahia","sequence":"first","affiliation":[{"name":"1Division of Hematology and Medical Oncology, Department of Medicine, Mays Cancer Center, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roderick","family":"Clifton-Bligh","sequence":"additional","affiliation":[{"name":"2Department of Endocrinology, Royal North Shore Hospital, Northern Clinical School, Kolling Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Paule","family":"Gimenez-Roqueplo","sequence":"additional","affiliation":[{"name":"4AP-HP, H\u00f4pital Europ\u00e9en Georges Pompidou, Genetics Department, Paris, France"},{"name":"5Human Cancer Genetics Program, Spanish National Cancer Research Center, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mercedes","family":"Robledo","sequence":"additional","affiliation":[{"name":"4AP-HP, H\u00f4pital Europ\u00e9en Georges Pompidou, Genetics Department, Paris, France"},{"name":"5Human Cancer Genetics Program, Spanish National Cancer Research Center, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilo","family":"Jimenez","sequence":"additional","affiliation":[{"name":"6Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","container-title":["Endocrine-Related Cancer"],"original-title":[],"link":[{"URL":"https:\/\/erc.bioscientifica.com\/view\/journals\/erc\/27\/8\/ERC-19-0435.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/erc.bioscientifica.com\/downloadpdf\/journals\/erc\/27\/8\/ERC-19-0435.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:55:31Z","timestamp":1784555731000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/erc\/article\/27\/8\/T41-T52\/25443"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8]]},"references-count":0,"journal-issue":{"issue":"8"},"URL":"https:\/\/doi.org\/10.1530\/erc-19-0435","relation":{},"ISSN":["1351-0088","1479-6821"],"issn-type":[{"value":"1351-0088","type":"print"},{"value":"1479-6821","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8]]}}}