Targeting MAPK (Ras/ERK) and PI3K/Akt pathways in pituitary tumorigenesis.

BACKGROUND: Pituitary adenomas are common intracranial neoplasms, comprising 10 - 15% of all brain tumors. Data from autopsy studies suggest that pituitary adenomas develop in 17 - 25% of the population. Nevertheless, the pathogenesis of sporadic pituitary tumors still remains obscure. OBJECTIVE: In this review, the roles of MAPK (mainly Ras/extracellular signal-regulated protein kinase (ERK)) and PI3K/Akt signaling pathways in pituitary tumorigenesis are summarised. METHODS: A full data search was performed through PubMed over the years 2000 - 2009 with key words 'pituitary, pituitary tumor, molecular biology, Akt, MAPK, PI3K, ERK', and all relevant publications have been included, together with selected publications prior to that date. Growth factor receptor mutations and overexpression, G protein mutations, other signaling pathway abnormalities or genetic syndromes associated with pituitary tumors are not discussed as these topics are behind the scope of this review. CONCLUSIONS: There are preclinical data and human pituitary tumor studies that are compatible with increased Ras/ERK and/or PI3K/Akt pathway activity in pituitary tumors. Future research focusing on scaffold proteins and signaling modulators regulating these pathways may help identify the initiating transforming events and accordingly new strategies may be developed targeting these pathways in pituitary tumors