Targeted Therapies in Pheochromocytoma and Paraganglioma

J Clin Endocrinol Metab. 2022 Nov 23;107(11):2963-2972. doi: 10.1210/clinem/dgac471.


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 [HIF2α] inhibitors, tumor vaccination together with checkpoint inhibitors, antiangiogenic therapies, kinase signaling inhibitors) are under evaluation in clinical trials. The HIF2α 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.

Keywords: metastatic; molecular targeted therapy; paraganglioma; pheochromocytoma.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Gland Neoplasms* / drug therapy
  • Adrenal Gland Neoplasms* / pathology
  • Humans
  • Paraganglioma* / drug therapy
  • Paraganglioma* / pathology
  • Pheochromocytoma* / drug therapy
  • Pheochromocytoma* / pathology
  • Randomized Controlled Trials as Topic
  • Sunitinib / therapeutic use
  • Temozolomide / therapeutic use


  • cabozantinib
  • Sunitinib
  • Temozolomide