Informace o publikaci
The EurOPDX consortium: Sharing patient tumor-derived xenografts for collaborative multicentric preclinical trials.
|Popis||The EurOPDX Consortium is an initiative of translational and clinical researchers from 14 cancer centers and universities across 9 European countries, with the common goal of creating a network of clinically relevant models of human cancer, and in particular patient-derived xenograft (PDX) models. PDX models, which are generated by transplantation into an immunodeficient mouse of a patient's tumor obtained fresh from surgery, are broadly implemented for all cancer pathologies by translational laboratories (Tentler et al., 2012). Grafted tumors have been shown to maintain high similarities with the original patient tumor. Hence, preclinical trials in large panels of models recapitulating the intertumor heterogeneity of human cancer have been shown to reproduce data obtained in clinical trials (Bertotti et al., 2011; Julien et al., 2012). The primary goal of the EurOPDX Consortium is to share PDX models and perform collaborative multicenter and multipathology "xeno patient" trials within molecularly defined tumor subsets, resulting in hypothesis-driven personalized medicine strategies for cancer patients. Altogether, the Consortium displays a panel of more than 1,500 PDX subcutaneous and orthotopic models in more than 30 pathologies, including for instance 640 models obtained from primary tumors or metastases of colorectal cancer, 200 models of pancreatic cancer, and over 120 models of breast cancer. The characterization of models will be harmonized and will include deep molecular profiling and pharmacogenomic data corresponding to current anticancer therapies. Through implementation of a shared database and the emergence of a common biobank of patient-derived viable cancer specimens, the Consortium will use characterization data to identify novel strategies for pinpointing new targets and overcoming drug resistance, and will validate therapeutic hits in collaborative multicentric preclinical trials. Best practices for the performance of such trials in mice will be implemented, with the goal of advancing their predictivity for success in the clinic. The Consortium will also generate new PDX models and integrate complementary models such as ex vivo 2D and 3D assays to achieve research goals. Implementing PDX models in the discovery of predictive biomarkers for targeted therapies will be a key objective. This initiative will create a pipeline that will greatly accelerate and advance the development of novel therapeutic strategies and their validation for cancer treatment, through more predictive preclinical or "co-clinical" data. Through this collaborative effort that is to our knowledge, unique in Europe, and the participation of pharmaceutical companies and SMEs involved in drug development, we aim to reduce the duplication of efforts in oncology drug development, ultimately improving the quality of life and overall survival of cancer patients.|