P4 - Development of patient-derived xenograft models (PDX) of metastatic prostate cancer

Marie-Therese Haider, Lukas Böckelmann, Su Jung Oh-Hohenhorst and Tobias Lange
Institute of Anatomy and Experimental Morphology, University Medical Center Hamburg-Eppendorf

In prostate cancer, as in many other tumor entities, a dominant source for research is the use of cell line-based tumor models. These cell lines were originally developed from clinical metastatic or primary tumor lesions and helped to understand underlying mechanisms of tumor formation, invasion, and drug resistance. However, cell line-based experiments have their limitation in years, sometimes decades, of two-dimensional in vitro-cultivation of these cell lines. To overcome the problem of artificially rendered tumor characteristics and genomic alterations, the use of freshly prepared tumor material in patient-derived xenograft (PDX) models emerged as a powerful tool to more accurately reflect the situation in patients. This is with special regard to better reproducing the metastatic cascade in such models.

In the past, our group was able to successfully develop a new PDX model by transplanting freshly resected tumor material from a prostate cancer patient onto immunodeficient mice. With the tumor being derived from a castration-resistant prostate cancer patient who underwent radical prostatectomy and subsequent androgen-deprivation therapy, this new model resembles clinical reality much better and tumors spontaneously disseminated to distant sites.

The generation of new, spontaneously metastasizing PDX models is an ongoing effort in our group with special regard to castration-resistant PCa and aggressive variants of PCa from previously treated patients. These models could help in better understanding the mechanisms of transdifferentiation and treatment resistance. This effort is in strong collaboration with the research group of Prof. Dr. Gunhild von Amsberg and Dr. Wael Mansour, UKE.

Contact: to.lange@uke.de