Signaling Pathways in Pheochromocytomas and Paragangliomas: Prospects for Future Therapies

Overview

Journal Endocr Pathol

Specialties Endocrinology
Pathology

Date 2012 Mar 7

PMID 22391976

Citations 36

Authors

Svenja Nolting

Ashley B Grossman

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

The Molecular Classification of Pheochromocytomas and Paragangliomas: Discovering the Genomic and Immune Landscape of Metastatic Disease.

de Bresser C, de Krijger R Endocr Pathol. 2024; 35(4):279-292.

PMID: 39466488 PMC: 11659362. DOI: 10.1007/s12022-024-09830-3.

The Immune Landscape of Pheochromocytoma and Paraganglioma: Current Advances and Perspectives.

Uher O, Hadrava Vanova K, Taieb D, Calsina B, Robledo M, Clifton-Bligh R Endocr Rev. 2024; 45(4):521-552.

PMID: 38377172 PMC: 11244254. DOI: 10.1210/endrev/bnae005.

Management of Pheochromocytomas and Paragangliomas: A Case-Based Review of Clinical Aspects and Perspectives.

Sobocki B, Perdyan A, Szot O, Rutkowski J J Clin Med. 2022; 11(9).

PMID: 35566714 PMC: 9103340. DOI: 10.3390/jcm11092591.

Single-cell transcriptome analysis identifies a unique tumor cell type producing multiple hormones in ectopic ACTH and CRH secreting pheochromocytoma.

Zhang X, Lian P, Su M, Ji Z, Deng J, Zheng G Elife. 2021; 10.

PMID: 34905486 PMC: 8719890. DOI: 10.7554/eLife.68436.

Sunitinib Treatment for Advanced Paraganglioma: Case Report of a Novel SDHD Gene Mutation Variant and Systematic Review of the Literature.

Sesti F, Feola T, Puliani G, Centello R, Di Vito V, Bagni O Front Oncol. 2021; 11:677983.

PMID: 34221997 PMC: 8247584. DOI: 10.3389/fonc.2021.677983.

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