@article{b09df03d4e0f40a3998f51d9a8de7e1a,
title = "Antitumor effect of FGFR inhibitors on a novel cholangiocarcinoma patient derived xenograft mouse model endogenously expressing an FGFR2-CCDC6 fusion protein",
abstract = "Cholangiocarcinoma is a highly lethal cancer with limited therapeutic options. Recent genomic analysis of cholangiocarcinoma has revealed the presence of fibroblast growth factor receptor 2 (FGFR2) fusion proteins in up to 13% of intrahepatic cholangiocarcinoma (iCCA). FGFR fusions have been identified as a novel oncogenic and druggable target in a number of cancers. In this study, we established a novel cholangiocarcinoma patient derived xenograft (PDX) mouse model bearing an FGFR2-CCDC6 fusion protein from a metastatic lung nodule of an iCCA patient. Using this PDX model, we confirmed the ability of the FGFR inhibitors, ponatinib, dovitinib and BGJ398, to modulate FGFR signaling, inhibit cell proliferation and induce cell apoptosis in cholangiocarcinoma tumors harboring FGFR2 fusions. In addition, BGJ398 appeared to be superior in potency to ponatinib and dovitinib in this model. Our findings provide a strong rationale for the investigation of FGFR inhibitors, particularly BGJ398, as a therapeutic option for cholangiocarcinoma patients harboring FGFR2 fusions.",
keywords = "BGJ398, Dovitinib, FGFR2 fusion, Intrahepatic cholangiocarcinoma, Ponatinib",
author = "Yu Wang and Xiwei Ding and Shaoqing Wang and Moser, {Catherine D.} and Shaleh, {Hassan M.} and Mohamed, {Essa A.} and Roongruedee Chaiteerakij and Allotey, {Loretta K.} and Gang Chen and Katsuyuki Miyabe and McNulty, {Melissa S.} and Albert Ndzengue and {Barr Fritcher}, {Emily G.} and Knudson, {Ryan A.} and Greipp, {Patricia T.} and Clark, {Karl J.} and Torbenson, {Michael S.} and Kipp, {Benjamin R.} and Jie Zhou and Barrett, {Michael T.} and Gustafson, {Michael P.} and Alberts, {Steven R.} and Borad, {Mitesh J.} and Roberts, {Lewis R.}",
note = "Funding Information: This work was supported by the National Institutes of Health ( CA165076 to L.R.R.), the Mayo Clinic Center for Cell Signaling in Gastroenterology ( P30DK084567 ), the Mayo Clinic Cancer Center ( CA15083 ), ARIAD Pharmaceuticals , and The Cholangiocarcinoma Foundation . The authors thank Dr. Joseph M. Gozgit (ARIAD Pharmaceuticals Inc., Cambridge, MA) for helpful discussions and critical review of the manuscript. We also thank ARIAD Pharmaceuticals Inc. for providing ponatinib for this study. We thank the Mayo Cytogenetics Core and Darlene Knutson and Sara Kloft-Nelson for assistance with the FISH and G-banding analyses. The authors acknowledge the generous donation of the tissue sample from the patient without which this project would not be possible. Publisher Copyright: {\textcopyright} 2016",
year = "2016",
month = sep,
day = "28",
doi = "10.1016/j.canlet.2016.05.017",
language = "English (US)",
volume = "380",
pages = "163--173",
journal = "Cancer Letters",
issn = "0304-3835",
publisher = "Elsevier Ireland Ltd",
number = "1",
}