Dovitinib (TKI258) - A Novel Therapeutic Option in Advanced-Stage Endometrial Cancer?

Novel therapeutic options in human cancers, especially in advanced-stage tumors with a mutation in the putative target genes, has been recently applied [1,2]. One of the mostly investigated signaling pathways is the FGFR-pathway, playing a crucial role in various cellular processes, including proliferation and differentiation, angiogenesis, embyogenesis as well as tissue homeostasis [3,4]. The FGFR-signaling pathway consists of 4 highly-conserved FGFRs (named FGFR 1-4) and 18 ligands, which expression pattern is celland type-specific [3]. Interestingly, FGFR ligand binding leads to dimerization of the receptor and subsequently enzymatic kinase activity leading to downstream signaling pathway [3]. The expression of FGFs as well as their specific receptors has been investigated in normal endometrial cells during the menstrual cycle in humans and in animals, showing different expression patterns [5,6]. In particular, inhibition of the FGFR2-pathways leads to reduced cell growth as well as increased antitumor activity in endometrial cancer cells in vitro [7].