목적: The axis of Fibroblast Growth Factors (FGFs) / Fibroblast Growth Factor Receptors (FGFRs) has been implicated in malignant transformation, tumor mitogenesis, angiogenesis and chemoresistance. Even though the prevalence of FGFR1 mutation is reported to be low as about 5% in epithelial ovarian cancer (EOC), blocking this FGFs / FGFRs axis may be still intriguing treatment strategy for EOC since FGFR inhibitors are targeting not only cancer cells but also the tumor microenvironment. The aim of this study is to determine the effect of AZD4547, selective FGFR1, -2,and -3 inhibitor, on cell survival, apoptosis, invasion, and migration of EOC in vivo and in vitro. Also we investigated enriched genetic pathways which are related with response of AZD4547 in EOC patients through high-throughput sequencing (HTS). 방법: We used EOC cell lines (A2780, A2780-CP20, SKOV3ip1, SKOV3-TR, HeyA8, HeyA8-MDR, RMG1, RMG2, ES2) for in vivo. Orthotopic models with selected cell lines through in vivo and patient derived xenograft (PDX) models were used for in vivo. HTS was done on patients with recurrent EOC (n= 36) who had treatment of AZD4547 to investigate genetic signatures of responders vs. non-responders with AZD4547. 결과: FGFR1, -2 and -3 were highly expressed across all EOC cell lines. Among FGFs, FGF19 was significantly higher in A2780-CP20 cell line as compared to A2780, SKOV3ip1, and SKOV3-TR. In cell survival assay, AZD4547 showed cytotoxic effect in A2780, SKOV3ip1, and SKOV3-TR but not in A2780-CP20, in which FGF19 was significantly higher suggesting poor response of AZD454/ in cells with highly activated FGF/FGFR axis. The pattern of the effects of AZD4547 on cell apoptosis was similar with those of cell survival assay showing that AZD4547 induced apoptosis was not observed in A2780-CP20 but the other cell lines. With A2780 and SKOV3ip1 which showed cytotoxic effects with AZD4547, cell migration & invasion assays and in vivo were done. Migration and invasion of tumor cells were significantly prohibited with AZD4547 and tumor weights were significantly lower with the treatment of AZD4547 (Figure 1). The same results were observed in PDX model (Figure 2). Among 36 recurrent EOC patients, 18 patients showed resistance with AZD454 7 and MET and MYC pathways were highly activated in these patients. 결론: Our data suggest that inhibition of FGFs / FGFRs axis may be a potential treatment target for EOC patients. Activated MET or MYC pathways can be predictive markers for treatment of AZD454 7.