Endocrine Pathology

, Volume 23, Issue 1, pp 21–33 | Cite as

Signaling Pathways in Pheochromocytomas and Paragangliomas: Prospects for Future Therapies



There is currently no completely effective therapy available for metastatic pheochromocytomas or paragangliomas. Increasing understanding of the germline and somatic mutations leading to pheochromocytoma and paraganglioma development has revealed crucial insights into the molecular pathology of these tumors. A detailed understanding of the molecular pathway alterations giving rise to pheochromocytomas and paragangliomas should allow for the exploration and development of new effective molecular-targeted therapy options for this rare but frequently fatal malignancy. Molecular analysis has shown that pheochromocytoma/paraganglioma-promoting gene mutations can be divided into two major groups—clusters 1 and 2—following two different routes to tumorigenesis. Cluster 1 mutations are associated with pseudohypoxia and aberrant VEGF signaling while cluster 2 mutations are associated with abnormal activation of kinase signaling pathways such as PI3 kinase/AKT, RAS/RAF/ERK, and mTORC1/p70S6K suggesting relevant targets for novel molecular-targeted therapy approaches which will be discussed in detail in this chapter.


Pheochromocytomas Paragangliomas Signaling Cell lines Targeted therapies 

Supplementary material

12022_2012_9199_MOESM1_ESM.docx (39 kb)
Table 1Study comparisons (DOCX 38 kb)
12022_2012_9199_MOESM2_ESM.docx (19 kb)
Table 2Numbers of differentially expressed genes at p < 0.001 (DOCX 18 kb)
12022_2012_9199_MOESM3_ESM.docx (40 kb)
Table 3Selected gene ontology (GO) summaries (DOCX 39 kb)


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and DentistryQueen Mary University of LondonLondonUK
  2. 2.Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill HospitalUniversity of OxfordOxfordUK

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