Pancreatic cancer organoids recapitulate disease and allow personalized drug screening

E Driehuis, A Van Hoeck, K Moore… - Proceedings of the …, 2019 - National Acad Sciences
E Driehuis, A Van Hoeck, K Moore, S Kolders, HE Francies, MC Gulersonmez, ECA Stigter…
Proceedings of the National Academy of Sciences, 2019National Acad Sciences
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 …
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.
National Acad Sciences