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 targetMTAP(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.
Funder
American Association for Cancer Research
ZonMw
Welcome Trust
CRUK
Dutch Digestive foundation
Publisher
Proceedings of the National Academy of Sciences
Reference40 articles.
1. N. Howlader , A. Noone , M. Krapcho , D. Miller , K. Bishop , C. Kosary ., “SEER Cancer Statistics Review, 1975–2014” (National Cancer Institute, 2016).
2. Distal bile duct carcinomas and pancreatic ductal adenocarcinomas: Postulating a common tumor entity;Schmuck;Cancer Med.,2016
3. FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic Cancer
4. D. D. Von Hoff , T. Ervin , F. P. Arena , E. G. Chiorean , J. Infante , M Moore ., Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N. Engl J Med. 369, 1691–1703.
5. Human Pancreatic Tumor Organoids Reveal Loss of Stem Cell Niche Factor Dependence during Disease Progression
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