A new twist in neuroendocrine tumor research: Pacak-Zhuang syndrome, HIF-2 alpha as the major player in its pathogenesis and future therapeutic options

作者：Jochmanova Ivana^*; Lazurova Ivica

来源：Biomedical Papers-Olomouc, 2014, 158(2): 175-180.

DOI：10.5507/bp.2014.021

• hypoxia-inducible factor
• tumorigenesis
• pheochromocytoma
• paraganglioma
• Pacak-Zhuang syndrome

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 2 alpha gene (HIF2A) mutations.
Methods and 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-2 alpha in the PHEO/PGL development and these findings designate HIF, especially HIF-2 alpha, as a promising treatment target.

• 出版日期2014