Introduction to PDTX
In vitro cellular assays and in vivo xenograft models are traditionally used in anticancer drug development. However, it turned clear that artificially grown tumor cells or xenografts act dramatically different than clinical tumors. This led to the shift from cell line models to genetically engineered models (GEMs) and patient-derived tumor xenograft models (PDTXs) in the preclinical drug development, not only having better molecular similarity to the clinical disease, but providing similar microenvironment, metabolic and vascularization properties as well.
Our aim is to use this model bank in collaboration with other research groups interested in cancer drug development, tumor phenotype biomarker research, therapy resistance and sensitivity experiments. As reportedly 95% of drug candidates entering clinical trials fail, mostly becouse lack of effect and safety, we believe that using better models drastically reduce the unnecessary clinical testing cost during drug development.
We successfully developed our system to establish, archive and maintain PDTX models in immunodeficient (SCID or NSG) mice in order to provide hundreds of options to our partners to use the best preclinical models for in vivo drug testing. We also establish parallel cell lines from the models for the investigation of similarities and differences between cell cultures and serial xenografting.
The figures above show that PDTX tumours are preserving the morphological and immunohistochemical properties of the clinical tumor, while assessment of a derived cell line – similarly to other traditional cell line xenografts – comes along with a drastical change both tissue structure and molecular marker pattern.
Our workflow – PDTX establishment
We work in cooperation with 10 clinical oncology centers in Hungary in order to access various types of clinical tumor samples. Serial xenografting in immunodeficient mice, and biobanking of different outcome samples allows us to provide complete documentation about our PDTX models.
Our workflow – PDTX utilization
Based on our PDTX database, we are developing our online interface to see all relevant information about our models, including basic clinical data, results of past assays performed on the model, characterization of the model, and its availability. In vivo tumor experiments, molecular biology samples, or cell lines are equally reachable in order to optimize the tools for every research needs.
We are building our biobank to develop as much as 500 different PDTX models by the end of 2020. This ongoing project is open to any collaborations and drug development experiments.
In case you are interested in PDTX models, do not hesitate to contact us:
Dr. József Tóvári