Pancreatic cancer organoids recapitulate disease and allow personalized drug screening

Else Driehuis, Arne Van Hoeck, Kat Moore, Sigrid Kolders, Hayley E. Francies, M. Can Gulersonmez, Edwin C.A. Stigter, Boudewijn Burgering, Veerle Geurts, Ana Gracanin, Gergana Bounova, Folkert H. Morsink, Robert Vries, Sylvia Boj, Johan Van Es, G. Johan A. Offerhaus, Onno Kranenburg, Mathew J. Garnett, Lodewyk Wessels, Edwin CuppenLodewijk A.A. Brosens, Hans Clevers

Research output: Contribution to journalArticlepeer-review

244 Citations (Scopus)

Abstract

We report the derivation of 30 patient-derived organoid lines (PDOs) from tumors arising in the pancreas and distal bile duct. PDOs recapitulate tumor histology and contain genetic alterations typical of pancreatic cancer. In vitro testing of a panel of 76 therapeutic agents revealed sensitivities currently not exploited in the clinic, and underscores the importance of personalized approaches for effective cancer treatment. The PRMT5 inhibitor EZP015556, shown to target MTAP (a gene commonly lost in pancreatic cancer)-negative tumors, was validated as such, but also appeared to constitute an effective therapy for a subset of MTAP-positive tumors. Taken together, the work presented here provides a platform to identify novel therapeutics to target pancreatic tumor cells using PDOs.

Original languageEnglish
Pages (from-to)26580-26590
Number of pages11
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number52
DOIs
Publication statusPublished - 26 Dec 2019

Keywords

  • Biobank
  • Cancer
  • Organoids
  • Pancreatic cancer
  • Personalized medicine

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