@article{ee7cac7442a140b591a04333346444f5,
title = "Establishment of Patient-Derived Organoids and Drug Screening for Biliary Tract Carcinoma",
abstract = "Biliary tract carcinomas (BTCs) are among the most aggressive malignancies and have a poor prognosis. Here, we successfully established organoid lines derived from intrahepatic cholangiocarcinoma, gallbladder cancer, and neuroendocrine carcinoma of the ampulla of Vater. These organoids derived from BTCs were cultured stably for >1 year and closely recapitulated the histopathology, gene expression, and genetic alterations evident in the primary tumors. Gene expression profiling of the organoids revealed that SOX2 could be a potential prognostic biomarker for patients with BTC. We screened a compound library consisting of drugs used clinically for their ability to suppress organoids derived from BTCs and found that the antifungal drugs amorolfine and fenticonazole significantly suppressed the growth of organoids derived from BTCs with minimal toxicity to normal biliary epithelial cells. Patient-derived organoids may be a powerful research tool for the clarification of molecular pathogenesis and the discovery of biomarkers and therapeutic drugs for refractory cancers.",
keywords = "antifungal drug, biliary tract carcinoma, drug screening, gallbladder cancer, intrahepatic cholangiocarcinoma, neuroendocrine carcinoma of the ampulla of Vater, organoid culture",
author = "Yoshimasa Saito and Toshihide Muramatsu and Yae Kanai and Hidenori Ojima and Aoi Sukeda and Nobuyoshi Hiraoka and Eri Arai and Yuko Sugiyama and Juntaro Matsuzaki and Ryoei Uchida and Nao Yoshikawa and Ryo Furukawa and Hidetsugu Saito",
note = "Funding Information: A compound library of clinically used drugs was obtained from the Platform Project for Supporting Drug Discovery and Life Science Research from AMED under Grant Number JP17am0101086. Cells from organoid line #1 were plated (1.2 × 10 3 / well) and cultured for 4 days, and compounds were added to the culture medium at final concentration of 0.1 μM. After 6 days of treatment with the compounds, cell viability was examined by WST assay using the Cell Counting Kit-8 (Dojindo) in accordance with the manufacturer{\textquoteright}s instructions. We used 0.1% dimethyl sulfoxide (DMSO) as a control. When the ratio of the average level of cell viability in the presence of the compounds (n = 3) compared to the control (n = 3) was under 0.5, the suppressive effect was considered to be significant. Funding Information: This work was supported by a Keio University Special Grant-in-Aid for Innovative Collaborative Research Projects (to Y. Saito), JSPS KAKENHI grant no. JP17H03592 (to Y. Saito), and the Platform Project for Supporting Drug Discovery and Life Science Research from the AMED under grant no. JP17am0101086 . We thank Dr. Toshiro Sato (Keio University) for kind support and advice on organoid culture. Publisher Copyright: {\textcopyright} 2019 The Author(s)",
year = "2019",
month = apr,
day = "23",
doi = "10.1016/j.celrep.2019.03.088",
language = "English",
volume = "27",
pages = "1265--1276.e4",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "4",
}
