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

Chiara Raggi, Karim Fiaccadori, Mirella Pastore, Margherita Correnti, Benedetta Piombanti, Elisa Forti, Nadia Navari, Giovanni Abbadessa, Terence Hall, Annarita Destro, Luca Di Tommaso, Massimo Roncalli, Fanyin Meng, Shannon Glaser, Elisabetta Rovida, Caterina Peraldo-Neia, Paula Olaizola, Jesus M. Banales, Alessio Gerussi, Alessandra ElveviMichele Droz dit Busset, Sherrie Bhoori, Vincenzo Mazzaferro, Gianfranco Alpini, Fabio Marra, Pietro Invernizzi

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)2090-2101
Number of pages12
JournalAmerican Journal of Pathology
Volume189
Issue number10
DOIs
Publication statusPublished - Oct 2019

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Fibroblast Growth Factor Receptors
Cholangiocarcinoma
Receptor, Fibroblast Growth Factor, Type 2
Cell Line
Epithelial-Mesenchymal Transition
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
Growth
Western Blotting
Immunohistochemistry

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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Antitumor Activity of a Novel Fibroblast Growth Factor Receptor Inhibitor for Intrahepatic Cholangiocarcinoma. / Raggi, Chiara; Fiaccadori, Karim; Pastore, Mirella; Correnti, Margherita; Piombanti, Benedetta; Forti, Elisa; Navari, Nadia; Abbadessa, Giovanni; Hall, Terence; Destro, Annarita; Di Tommaso, Luca; Roncalli, Massimo; Meng, Fanyin; Glaser, Shannon; Rovida, Elisabetta; Peraldo-Neia, Caterina; Olaizola, Paula; Banales, Jesus M.; Gerussi, Alessio; Elvevi, Alessandra; Droz dit Busset, Michele; Bhoori, Sherrie; Mazzaferro, Vincenzo; Alpini, Gianfranco; Marra, Fabio; Invernizzi, Pietro.

In: American Journal of Pathology, Vol. 189, No. 10, 10.2019, p. 2090-2101.

Research output: Contribution to journalArticle

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, JM, Gerussi, A, Elvevi, A, Droz dit Busset, M, Bhoori, S, Mazzaferro, V, Alpini, G, Marra, F & Invernizzi, P 2019, 'Antitumor Activity of a Novel Fibroblast Growth Factor Receptor Inhibitor for Intrahepatic Cholangiocarcinoma', American Journal of Pathology, vol. 189, no. 10, pp. 2090-2101. https://doi.org/10.1016/j.ajpath.2019.06.007
Raggi, Chiara ; Fiaccadori, Karim ; Pastore, Mirella ; Correnti, Margherita ; Piombanti, Benedetta ; Forti, Elisa ; Navari, Nadia ; Abbadessa, Giovanni ; Hall, Terence ; Destro, Annarita ; Di Tommaso, Luca ; Roncalli, Massimo ; Meng, Fanyin ; Glaser, Shannon ; Rovida, Elisabetta ; Peraldo-Neia, Caterina ; Olaizola, Paula ; Banales, Jesus M. ; Gerussi, Alessio ; Elvevi, Alessandra ; Droz dit Busset, Michele ; Bhoori, Sherrie ; Mazzaferro, Vincenzo ; Alpini, Gianfranco ; Marra, Fabio ; Invernizzi, Pietro. / Antitumor Activity of a Novel Fibroblast Growth Factor Receptor Inhibitor for Intrahepatic Cholangiocarcinoma. In: American Journal of Pathology. 2019 ; Vol. 189, No. 10. pp. 2090-2101.
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AU - Olaizola, Paula

AU - Banales, Jesus M.

AU - Gerussi, Alessio

AU - Elvevi, Alessandra

AU - Droz dit Busset, Michele

AU - Bhoori, Sherrie

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