Pancreatic cancer organoids recapitulate disease and allow personalized drug screening
Cet article présente une biobanque de 30 organoïdes de cancers pancréatiques disposant de données histologiques et génomiques et permettant d'identifier des agents thérapeutiques
We describe a biobank of patient-derived pancreatic cancer organoids, characterized by whole-genome DNA sequencing, RNA sequencing, and histology. The organoid biobank will be made publicly available and thus can serve as a resource for others. Pancreatic cancer organoids have been described previously; however, here we expose organoids to extensive drug screens to reveal unique drug sensitivity profiles for individual organoid lines. These findings underscore the importance of personalized approaches when using targeted agents to treat cancer in the clinic.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.
Proceedings of the National Academy of Sciences , résumé, 2018