02561nas a2200433   4500000000100000000000100001008004100002260001200043653002600055653002100081653003300102653003700135653001500172653000800187653003700195653001100232653001400243653002500257653002300282653001100305653001300316653001500329653001500344100001600359700001800375700002500393700002000418700001800438700001500456700002000471700001800491700001800509700002200527245011500549300001200664490000700676520143000683022001402113       2018                            d  c2018-0710aAntineoplastic Agents10aCell Line, Tumor10aDrug Evaluation, Preclinical10aDrug Screening Assays, Antitumor10aHT29 Cells10aHTS10aHigh-Throughput Screening Assays10aHumans10aorganoids10aPancreatic Neoplasms10aPrecision Medicine10aCancer10aorganoid10apancreatic10aphenotypic1 aShurong Hou1 aHervé Tiriac1 aBanu Priya Sridharan1 aLouis Scampavia1 aFranck Madoux1 aJan Seldin1 aGlauco R. Souza1 aDonald Watson1 aDavid Tuveson1 aTimothy P. Spicer00aAdvanced Development of Primary Pancreatic Organoid Tumor Models for High-Throughput Phenotypic Drug Screening  a574-5840 v233 aTraditional high-throughput drug screening in oncology routinely relies on two-dimensional (2D) cell models, which inadequately recapitulate the physiologic context of cancer. Three-dimensional (3D) cell models are thought to better mimic the complexity of in vivo tumors. Numerous methods to culture 3D organoids have been described, but most are nonhomogeneous and expensive, and hence impractical for high-throughput screening (HTS) purposes. Here we describe an HTS-compatible method that enables the consistent production of organoids in standard flat-bottom 384- and 1536-well plates by combining the use of a cell-repellent surface with a bioprinting technology incorporating magnetic force. We validated this homogeneous process by evaluating the effects of well-characterized anticancer agents against four patient-derived pancreatic cancer KRAS mutant-associated primary cells, including cancer-associated fibroblasts. This technology was tested for its compatibility with HTS automation by completing a cytotoxicity pilot screen of ~3300 approved drugs. To highlight the benefits of the 3D format, we performed this pilot screen in parallel in both the 2D and 3D assays. These data indicate that this technique can be readily applied to support large-scale drug screening relying on clinically relevant, ex vivo 3D tumor models directly harvested from patients, an important milestone toward personalized medicine.  a2472-5560