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Targeted Therapies in Pheochromocytoma and Paraganglioma
Ludwig Maximilian Univ Munich, Univ Hosp, Dept Internal Med 4, LMU Klinikum, D-80336 Munich, Germany..ORCID iD: 0000-0002-7795-1395
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.ORCID iD: 0000-0003-0677-4894
Ludwig Maximilian Univ Munich, Univ Hosp, Dept Internal Med 4, LMU Klinikum, D-80336 Munich, Germany.;Univ Hosp Zurich USZ, Dept Endocrinol Diabetol & Clin Nutr, Ramistr 100, CH-8091 Zurich, Switzerland.;Univ Zurich UZH, Ramistr 100, CH-8091 Zurich, Switzerland..ORCID iD: 0000-0001-7826-3984
Univ Oxford, Green Templeton Coll, Oxford OX2 6HG, England.;Royal Free Hosp, ENETS Ctr Excellence, NET Unit, London NW3 2QG, England..
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2022 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 107, no 11, p. 2963-2972Article, review/survey (Refereed) Published
Abstract [en]

Molecular targeted therapy plays an increasingly important role in the treatment of metastatic pheochromocytomas and paragangliomas (PPGLs), which are rare tumors but remain difficult to treat. This mini-review provides an overview of established molecular targeted therapies in present use, and perspectives on those currently under development and evaluation in clinical trials. Recently published research articles, guidelines, and expert views on molecular targeted therapies in PPGLs are systematically reviewed and summarized. Some tyrosine kinase inhibitors (sunitinib, cabozantinib) are already in clinical use with some promising results, but without formal approval for the treatment of PPGLs. Sunitinib is the only therapeutic option which has been investigated in a randomized placebo-controlled clinical trial. It is clinically used as a first-, second-, or third-line therapeutic option for the treatment of progressive metastatic PPGLs. Some other promising molecular targeted therapies (hypoxia-inducible factor 2 alpha [HIF2 alpha] inhibitors, tumor vaccination together with checkpoint inhibitors, antiangiogenic therapies, kinase signaling inhibitors) are under evaluation in clinical trials. The HIF2 alpha inhibitor belzutifan may prove to be particularly interesting for cluster 1B-/VHL/EPAS1-related PPGLs, whereas antiangiogenic therapies seem to be primarily effective in cluster 1A-/SDHx-related PPGLs. Some combination therapies currently being evaluated in clinical trials, such as temozolomide/olaparib, temozolomide/talazoparib, or cabozantinib/atezolizumab, will provide data for novel therapy for metastatic PPGLs. It is likely that advances in such molecular targeted therapies will play an essential role in the future treatment of these tumors, with more personalized therapy options paving the way towards improved therapeutic outcomes.

Place, publisher, year, edition, pages
Oxford University Press, 2022. Vol. 107, no 11, p. 2963-2972
Keywords [en]
molecular targeted therapy, metastatic, pheochromocytoma, paraganglioma
National Category
Cancer and Oncology Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:uu:diva-497517DOI: 10.1210/clinem/dgac471ISI: 000844747200001PubMedID: 35973976OAI: oai:DiVA.org:uu-497517DiVA, id: diva2:1740528
Funder
German Research Foundation (DFG), 314061271 – TRR 205Available from: 2023-03-01 Created: 2023-03-01 Last updated: 2023-03-01Bibliographically approved

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Crona, Joakim

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