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Precision medicine in pheochromocytoma and paraganglioma: current and future concepts
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
NIH, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Med Neuroendocrinol Program Reprod & Adult E, Bethesda, MD USA..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
2016 (English)In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 286, no 6, 559-573 p.Article in journal, Meeting abstract (Refereed) Published
Abstract [en]

Pheochromocytoma and paraganglioma (PPGL) are rare diseases but are also amongst the most characterized tumour types. Hence, patients with PPGL have greatly benefited from precision medicine for more than two decades. According to current molecular biology and genetics-based taxonomy, PPGL 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-mitogenic and anti-apoptotic 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 PPGL syndromes require specific approaches for optimal diagnosis and localization of various syndrome-related tumours. Genotype-tailored treatment options, follow-up and preventive care are being investigated. Future new developments in precision medicine for PPGL 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-scale 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.

Place, publisher, year, edition, pages
2016. Vol. 286, no 6, 559-573 p.
Keyword [en]
cancer metabolism, neuroendocrine tumours, paraganglioma, personalized medicine, pheochromocytoma, precision medicine
National Category
Surgery Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-311489DOI: 10.1111/joim.12507ISI: 000388573300004PubMedID: 27165774OAI: oai:DiVA.org:uu-311489DiVA: diva2:1060576
Conference
Symposium on New Genetics with Impact on Treatment of Endocrine Tumour Disease, JUN 04-05, 2015, Uppsala, SWEDEN
Available from: 2016-12-29 Created: 2016-12-28 Last updated: 2016-12-29Bibliographically approved

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Björklund, PeymanCrona, Joakim
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