Mutations in fibroblast growth factor receptor 2 (FGFR2) have been recently 
described as a molecular-specific feature in endometrial carcinomas and the 
presence of activated FGFR2 mutations is associated with poor prognosis. For 
that reason, inhibition of FGFR2 could be a therapeutic target in the treatment 
of endometriod carcinomas. In this work, we investigated the antitumoral 
activity of dovitinib (a multiple kinase inhibitor) in human endometrial cancer 
cell (ECC) lines. We found that dovitinib caused cell growth arrest, loss of 
clonogenic growth, and cell-cycle arrest in FGFR2-mutated ECCs in in vitro and 
in vivo experiments. Next, we investigated the mechanistic basis of dovitinib 
effects. We could determine that dovitinib modified expression levels of 
well-known key cell-cycle regulatory proteins that induce cellular senescence. 
To further investigate the role of dovitinib, we analyzed its effect on estrogen 
receptor α (ER-α) expression. Surprisingly, we discovered that dovitinib 
enhances ER-α expression in FGFR2-mutant ECCs. Because blocking one signaling 
pathway is often not sufficient to cause total tumor regression and the 
effectiveness of individual inhibitors is often short-lived, we examined the 
impact of targeting FGFR2 with dovitinib in combination with a selective ER 
antagonist, fulvestrant (ICI182.780). Combination of dovitinib plus ICI182.780 
resulted in a significantly higher inhibition of cell growth than dovitinib 
treatment alone. These findings suggest that combinatory therapies using 
dovitinib plus ICI182.780 treatment can be truly effective in patients with 
endometrial carcinomas carrying FGFR2 mutations.