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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 Cuppen, Lodewijk A A Brosens, Hans Clevers
Proceedings of the National Academy of Sciences of the United States of America 2019 December 9
31818951
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.

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