Establishment of Patient-Derived Organoids and Drug Screening for Biliary Tract Carcinoma

Yoshimasa Saito, Toshihide Muramatsu, Yae Kanai, Hidenori Ojima, Aoi Sukeda, Nobuyoshi Hiraoka, Eri Arai, Yuko Sugiyama, Juntaro Matsuzaki, Ryoei Uchida, Nao Yoshikawa, Ryo Furukawa, Hidetsugu Saito

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1265-1276.e4
JournalCell Reports
Volume27
Issue number4
DOIs
Publication statusPublished - 2019 Apr 23

Keywords

  • antifungal drug
  • biliary tract carcinoma
  • drug screening
  • gallbladder cancer
  • intrahepatic cholangiocarcinoma
  • neuroendocrine carcinoma of the ampulla of Vater
  • organoid culture

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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