A new twist in neuroendocrine tumor research: Pacak-Zhuang syndrome, HIF-2α as the major player in its pathogenesis and future therapeutic options.
Backround. There is increasing evidence of the role of hypoxia or pseudohypoxia in tumorigenesis, including pheochromocytoma (PHEO) and paraganglioma (PGL). (Pseudo)hypoxia leads to activation of hypoxia-inducible transcription factors (HIFs) and thus, promotes the transcription of hypoxia-responsive genes which are involved in tumorigenesis. Recently identified is a new syndrome consisting of multiple and recurrent PGLs or PHEOs, somatostatinoma, and congenital polycythemia, due to somatic hypoxia-inducible factor 2α gene (HIF2A) mutations.


RESULTS
PubMed and Web of Science online databases were used to search reviews and original articles on the HIF, PHEO/PGL, and Pacak-Zhuang syndrome.


CONCLUSIONS
The novel somatic and germline gain-of-function HIF2A mutations described latterly emphasize the role of the HIF-2α in the PHEO/PGL development and these findings designate HIF, especially HIF-2α, as a promising treatment target.
st Department of Internal Medicine, Medical Faculty, P.J. Safarik University, Trieda SNP 1, 04011, Kosice, Slovak Republic.
Ivana
I
Jochmanova
Ivica
I
Lazurova
D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D063646:Carcinogenesis / Q000235:genetics; D006801:Humans; D009154:Mutation; D010235:Paraganglioma / Q000188:drug therapy / Q000235:genetics*; D011086:Polycythemia / Q000151:congenital / Q000188:drug therapy / Q000235:genetics*; D013005:Somatostatinoma / Q000188:drug therapy / Q000235:genetics*; D013577:Syndrome; D000099162:Endothelial PAS Domain-Containing Protein 1
D051792:Basic Helix-Loop-Helix Proteins; D000099162:Endothelial PAS Domain-Containing Protein 1