Introduction

Prostate and bladder cancer (PCa, BLCa) are highly frequent and metastatic urological malignancies. Relevant models for the study of tumor heterogeneity and drug resistance mechanisms are required. Patient-derived xenografts (PDX) comprise excellent tools for the maintenance of the molecular and functional properties of the original tumor and allow the long-term study and in vivo drug response assays. The objective is to establish PDX models from primary and metastatic PCa and BLCa, which are currently of limited availability, and to develop a platform for standardized characterization and drug response tests of the PDX tumors in vivo and in ex vivo tissue slices system.

Methods

PDX are generated by needle biopsy implantation (PCa, BLCa) subcutaneously in immunocompromised NOD SCID gamma mice. Tumors are serially transplanted in vivo. Histopathological and RNA analysis of the different passages of PDX tumors is performed to identify morphological and molecular similarities with the original tumor. As preclinical model, PDX tumors are maintained ex vivo (ten days) and used for drug testing assays based on the standard treatment used for primary types of PCa and BLCa.

Results

PDX models from primary and metastatic PCa and BLCa (BMURO) maintain morphology similar to the original tumor. Tumors (clinical specimens, PDXs) are tested in ex vivo drug response assays using our developed methodology on whole tissue slice culture system. Histological morphology of Lymph node-PCa tumor slices is affected by exposure to cytostatic agents (cabazitaxel, docetaxel). Bone metastasis BLCa (BMURO) tumor slices treated ex vivo with drug compounds exhibit morphological changes at the lowest concentrations of cisplatin and gemcitabine. Ongoing studies aim to address whether the ex vivo and in vivo PDX drug response recapitulates the individual drug response observed during clinical treatment prior to surgery.

Conclusions

Xenograft models are promising tools for the study of personalized treatment and drug resistance mechanisms in PCa and BLCa. The ex vivo drug response assays on PDX tumor slices represent an experimental screening platform of patient-specific drug responses.

Funding

Swiss National Funds