Fibroblast growth factor receptor 2 (FGFR2) might have an important role in the pathogenesis and biology of cholangiocarcinoma (CCA). We examined FGFR expression in CCA tumor specimens obtained from patients and CCA cell lines, and then determined the effects of the novel FGFR inhibitor, derazantinib (DZB; formally, ARQ 087), which is currently in clinical phase 2 trials for intrahepatic CCA. DZB inhibited the growth of CCA cell lines in a dose-dependent manner, and extracellular signal-regulated kinase 1/2 and AKT. It also activated apoptotic and cell growth arrest signaling. DZB reduced the in vitro invasiveness and the expression of key epithelial-mesenchymal transition genes. The in vitro data correlated with the expression of FGFRs in human CCA specimens by immunohistochemistry (FGFR1, 30% positive; and FGFR2, 65% positive) and the CCA cell lines assayed by Western blot analysis. These correlated in vitro studies suggest that FGFR may play an important role in the pathogenesis and biology of CCA. Our findings support the notion that FGFR inhibitors, like DZB, should be further evaluated at the clinical stage as targeted therapy for CCA treatment.

Raggi, C., Fiaccadori, K., Pastore, M., Correnti, M., Piombanti, B., Forti, E., et al. (2019). Antitumor Activity of a Novel Fibroblast Growth Factor Receptor Inhibitor for Intrahepatic Cholangiocarcinoma. THE AMERICAN JOURNAL OF PATHOLOGY, 189(10), 2090-2101 [10.1016/j.ajpath.2019.06.007].

Antitumor Activity of a Novel Fibroblast Growth Factor Receptor Inhibitor for Intrahepatic Cholangiocarcinoma

Gerussi, Alessio
Membro del Collaboration Group
;
Invernizzi, Pietro
Ultimo
Membro del Collaboration Group
2019

Abstract

Fibroblast growth factor receptor 2 (FGFR2) might have an important role in the pathogenesis and biology of cholangiocarcinoma (CCA). We examined FGFR expression in CCA tumor specimens obtained from patients and CCA cell lines, and then determined the effects of the novel FGFR inhibitor, derazantinib (DZB; formally, ARQ 087), which is currently in clinical phase 2 trials for intrahepatic CCA. DZB inhibited the growth of CCA cell lines in a dose-dependent manner, and extracellular signal-regulated kinase 1/2 and AKT. It also activated apoptotic and cell growth arrest signaling. DZB reduced the in vitro invasiveness and the expression of key epithelial-mesenchymal transition genes. The in vitro data correlated with the expression of FGFRs in human CCA specimens by immunohistochemistry (FGFR1, 30% positive; and FGFR2, 65% positive) and the CCA cell lines assayed by Western blot analysis. These correlated in vitro studies suggest that FGFR may play an important role in the pathogenesis and biology of CCA. Our findings support the notion that FGFR inhibitors, like DZB, should be further evaluated at the clinical stage as targeted therapy for CCA treatment.
Articolo in rivista - Articolo scientifico
Cholangiocarcinoma
English
2090
2101
12
Published: OCT 2019
Raggi, C., Fiaccadori, K., Pastore, M., Correnti, M., Piombanti, B., Forti, E., et al. (2019). Antitumor Activity of a Novel Fibroblast Growth Factor Receptor Inhibitor for Intrahepatic Cholangiocarcinoma. THE AMERICAN JOURNAL OF PATHOLOGY, 189(10), 2090-2101 [10.1016/j.ajpath.2019.06.007].
Raggi, C; Fiaccadori, K; Pastore, M; Correnti, M; Piombanti, B; Forti, E; Navari, N; Abbadessa, G; Hall, T; Destro, A; Di Tommaso, L; Roncalli, M; Meng, F; Glaser, S; Rovida, E; Peraldo-Neia, C; Olaizola, P; Banales, J; Gerussi, A; Elvevi, A; Droz Dit Busset, M; Bhoori, S; Mazzaferro, V; Alpini, G; Marra, F; Invernizzi, P
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/240048
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