Subtyping Of Pancreatic Cancer Patient Derived Xenograft Tumors And Implications For Anticancer Agent Testing

Despite improvements in treatment, pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal cancers, with a continuous increase in incidence emphasizing the need for further research and therapeutic development. In recent years, we have developed a collection of u003e40 patient-derived xenograft (PDX) models from PDAC. In order to determine their relevance for anticancer agent testing, we extensively characterized our models for histology features, whole exome mutations (Hiseq 2000), chromosome rearrangements, gene copy number variations (Affymetrix SNP6) and gene expression (Affymetrix U133 Plus2.0). PDAC from 65 patients were implanted into immuno-compromised mice, resulting in the development of 42 PDX models (success rate 65%). The PDAC from which models were established included moderate and poorly differentiated tumors and were heterogeneous for stroma content. In patient tumors, we showed fibroblast activation but not stroma content predicted poor patient outcome (p Extensive characterization of our PDAC_PDX collection revealed similarities with patient tumors with regards of histology features including stroma content and fibroblast activation. At molecular level, the models showed similar genomic and transcriptomic patterns as those reported for patient PDAC, altogether, proving the value of this collection for drug development investigations. Citation Format: Peter Bronsert, Tim Kees, Bruno Zeitouni, Anne-Lise Peille, Manuel Landesfeind, Heinz-Herbert Fiebig, Simon Kuesters, Vincent Vuaroqueaux. Subtyping of pancreatic cancer patient-derived xenograft tumors and implications for anticancer agent testing. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 639.