Abstract 3846: Imodi initiative: A novel holistic and integrative approach with patient-derived tumor models against pancreatic cancer
Authors: Iovanna Juan , Dussetti Nelson , Meyer-losic Florence , Vacon Françoise Le , Calvet Loreley , Forraz Nico , Dhondt Kevin , Kuras Mariana , Lautrette Christophe , Tabone-Eglinger Séverine , Vaglio Philippe , Duchamp Olivier 
Published: July 2017

Patient-derived xenografts (PDX) are appearing as a prime approach for preclinical studies despite being insufficiently characterized as a model of the human disease and its diversity. Many reports support that xenografts from PDX in mice recapitulate well the molecular diversity, cellular heterogeneity, and histology seen in patient tumors. However, several lacks such as the limited clinical diversity of the PDXs, the absence of human drug metabolism and the reduced immune system are limiting the predictive values of these PDX models. To set-up a holistic integration of these criticisms, we have associated efforts from public hospitals, academic groups, biotechs and private pharmaceutical companies with the financial support of the French Ministry of Industry.

First, to improve the clinical diversity of the PDX collections, surgical specimens or biopsies from patients with 9 different types of cancers (pancreas, lung, breast, ovary, liver, prostate, AML, myeloma, lymphoma) are collected since 2013 to establish large collections of PDXs in mice. In addition, primary cultures of cells from these samples are established leading to a collection of cell lines from the stroma and the tumoral compartment. Pancreatic PDX from primary tumors and its metastasis were obtained from either surgery or by endoscopic ultrasound-guided fine needle aspirate and therefore representing a bio-banking with a unique diversity. The established pancreatic models are being evaluated for histological, extensive molecular characteristics and in vitro and in vivo sensitivities to relevant anticancer drugs. We found i/ a variable sensitivity on PDX-derived cells when treated in vitro with increasing concentrations of clinically relevant drugs; ii/ that sensitivity to one drug does not predict the sensitivity to the another one; and iii/ sensitivity to drugs in vivo reproduce, but not systematically, the results in vitro. To be noted, no correlation between sensitivity and genetic characteristics (mutations or CNV) or histological proprieties was found. All model characteristics are being compiled in a web-based database for efficient features search and interconnection.

Second, we are generating mice with humanized liver showing human drug pharmacokinetic and metabolism profiles

We will present the first pancreatic cancer models characterized and will discuss their usefulness and chance to bring benefit to patients via this holistic strategy developed within IMODI initiative.

Citation Format: Juan Iovanna, Nelson Dussetti, Florence Meyer-losic, Françoise Le Vacon, Loreley Calvet, Nico Forraz, Kevin Dhondt, Mariana Kuras, Christophe Lautrette, Séverine Tabone-Eglinger, Philippe Vaglio, Olivier Duchamp. Imodi initiative: A novel holistic and integrative approach with patient-derived tumor models against pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3846. doi:10.1158/1538-7445.AM2017-3846