In the last years, the scientific community working in the field of preclinical cancer research has realized the importance of mutualizing efforts and exchanging models and expertise to avoid duplication. In addition, a number of publications have pointed out the necessity of raising standards in preclinical cancer research to significantly improve the success of drug development in the field of oncology. To improve the robustness of data, preclinical studies need to be conducted with the rigor and challenges of clinical trials. Patient-derived tumor xenografts (PDXs) are today recognized as very relevant preclinical cancer models, however, they are very time-consuming and consequently very expensive.
Based on the valuable collaborations already established by some of the teams at the origin of this initiative, the increasing interest in these models in the academic and industrial arena, the necessity of raising standards in preclinical studies, and the need for covering as best as possible the patient’s tumour heterogeneity, a first meeting for multicentre discussion was organised at Institut Curie (Paris, France) in January 2013.
This first meeting already gathered 14 cancer centers and universities across 9 European countries and confirmed the high interest of all to engage in a joint initiative focusing on clinically relevant models of cancer.
Since then, 2 additional cancer centers joined including the Weill Cornell Medicine from the USA, and several additional meetings already allowed to clearly define the objectives of the Consortium, identify opportunities for funding, initiate discussions about common standards, and trigger a number of new collaborations for multicentre studies between the involved teams and additional scientists.
The main objectives of the consortium are:
– Create a multidisciplinary network of academic researchers in preclinical and translational oncology, clinical oncologists, pathologists, biostatisticians and bioinformaticians with a common goal of harnessing clinically relevant models of cancer, and in particular PDXs, and avoiding duplication of efforts. The network displays a wide range of expertise in technological platforms (e.g. NGS, molecular imaging…);
– Share PDX models and harmonize characterization and annotation of the models in a common database implemented for the Consortium collection;
– Elucidate standard operating procedures and harmonize working practices for implementation of PDX models, biobanking, biostatistics, protocol design and logistics for multicentre xenopatient trials, data analyses and reporting, with the goal to improve the reproducibility and predictability of preclinical and co-clinical studies;
– Perform research programs aiming in particular at i) a better characterisation of the models, ii) the development of new methodologies to overcome current limits of PDXs (e.g. humanisation strategies), iii) the implementation of new models in specific cancer subtypes to increase the representativeness of the collection, metastatic models or models resistant to standard therapies, iv) the development of complementary models for integration in innovative preclinical screening strategies (e.g. ex vivo 2D and 3D assays with PDX-derived primary cell cultures), v) the identification of new targets and novel therapeutic strategies for overcoming drug resistance, and vi) the discovery of predictive biomarkers for targeted therapies;
– Perform proof-of-concept collaborative multicentre and multipathology xenopatient preclinical trials for novel anticancer drugs or combinatorial strategies, within molecularly-defined tumor subsets and on a population scale, using the standards agreed, as a prelude for prospective clinical trials in humans. The Consortium will also perform co-clinical trials;
– Make publicly available as much as possible the results and data obtained from the work performed, to further reduce duplication of efforts within the scientific community;
– Teach young researchers state-of-the-art techniques related to PDX models and preclinical drug development;
– Participate in the improvement of the drug development process in oncology through more predictive preclinical and co-clinical studies, and ultimately contribute to the approval of new and effective therapeutic strategies for cancer patients.
The Consortium is working on a collaborative spirit, between EurOPDX members but also with other academic institutions, pharmaceuticals, and biotechs, and is not intended for performing any fee for service activities.