{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:49:10Z","timestamp":1790254150245,"version":"4.1.0"},"reference-count":147,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,5,10]],"date-time":"2016-05-10T00:00:00Z","timestamp":1462838400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Intern Med"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Pheochromocytoma and paraganglioma (\n                    <jats:styled-content style=\"fixed-case\">PPGL<\/jats:styled-content>\n                    ) are rare diseases but are also amongst the most characterized tumour types. Hence, patients with\n                    <jats:styled-content style=\"fixed-case\">PPGL<\/jats:styled-content>\n                    have greatly benefited from precision medicine for more than two decades. According to current molecular biology and genetics\u2010based taxonomy,\n                    <jats:styled-content style=\"fixed-case\">PPGL<\/jats:styled-content>\n                    can be divided into three different clusters characterized by: Krebs cycle reprogramming with oncometabolite accumulation or depletion (group 1a); activation of the (pseudo)hypoxia signalling pathway with increased tumour cell proliferation, invasiveness and migration (group 1b); and aberrant kinase signalling causing a pro\u2010mitogenic and anti\u2010apoptotic state (group 2). Categorization into these clusters is highly dependent on mutation subtypes. At least 12 different syndromes with distinct genetic causes, phenotypes and outcomes have been described. Genetic screening tests have a documented benefit, as different\n                    <jats:styled-content style=\"fixed-case\">PPGL<\/jats:styled-content>\n                    syndromes require specific approaches for optimal diagnosis and localization of various syndrome\u2010related tumours. Genotype\u2010tailored treatment options, follow\u2010up and preventive care are being investigated. Future new developments in precision medicine for\n                    <jats:styled-content style=\"fixed-case\">PPGL<\/jats:styled-content>\n                    will mainly focus on further identification of driver mechanisms behind both disease initiation and malignant progression. Identification of novel druggable targets and prospective validation of treatment options are eagerly awaited. To achieve these goals, we predict that collaborative large\u2010scale studies will be needed: Pheochromocytoma may provide an example for developing precision medicine in orphan diseases that could ultimately aid in similar efforts for other rare conditions.\n                  <\/jats:p>","DOI":"10.1111\/joim.12507","type":"journal-article","created":{"date-parts":[[2016,5,11]],"date-time":"2016-05-11T00:39:22Z","timestamp":1462927162000},"page":"559-573","source":"Crossref","is-referenced-by-count":51,"title":["Precision medicine in pheochromocytoma and paraganglioma: current and future concepts"],"prefix":"10.1111","volume":"280","author":[{"given":"P.","family":"Bj\u00f6rklund","sequence":"first","affiliation":[{"name":"Department of Surgical Sciences Uppsala University Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Pacak","sequence":"additional","affiliation":[{"name":"Section on Medical Neuroendocrinology Program in Reproductive and Adult Endocrinology Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) National Institutes of Health (NIH) Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Crona","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences Uppsala University Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,5,10]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"RonaldADR PhilippUH CharisE.Pathology and Genetics of Tumours of Endocrine Organs (IARC\/World Health Organization Classification of 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