Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 116, Issue 52, Pages 26580-26590Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1911273116
Keywords
pancreatic cancer; organoids; personalized medicine; cancer; biobank
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Funding
- Oncode Institute (Dutch Cancer Society)
- gravitation program CancerGenomiCs.nl from the Netherlands Organization for Scientific Research
- Stand Up to Cancer International Translational Cancer Research Grant
- program of the Entertainment Industry Foundation [SU2C-AACR-DT1213]
- ZonMw grant [116.006.103]
- Wellcome Trust [206194]
- Cancer Research UK [C44943/A22536]
- Dutch Digestive Foundation [MLDS CDG 14-020]
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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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