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. 2019 Dec 9;116(52):26580-26590.
doi: 10.1073/pnas.1911273116. Online ahead of print.

Pancreatic Cancer Organoids Recapitulate Disease and Allow Personalized Drug Screening

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Free PMC article

Pancreatic Cancer Organoids Recapitulate Disease and Allow Personalized Drug Screening

Else Driehuis et al. Proc Natl Acad Sci U S A. .
Free PMC article

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.

Keywords: biobank; cancer; organoids; pancreatic cancer; personalized medicine.

Conflict of interest statement

Competing interest statement: H.C. is an inventor listed on several patents related to organoid technology. H.C. is the (unpaid) Chief Scientific Officer of Hubrecht Organoid Technology, a cofounder of Surrozen, and a scientific advisory board member for Kallyope, Merus, and Decibel. H. Clevers is a nonexecutive board member of Roche and Genentech and a scientific advisor for Life Sciences Partners. E.D. is an inventor on a patent related to organoid technology.

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