Abstract 1060: Establishment of a panel of prostate patient derived xenograft (PDX) models and evaluation of anti-androgen therapy
Authors: Davis Jason , Oakden Anthony , Wrigley Jane , Roberts Chira , Qian W , Fan Bin , Collins A , Ouyang Davy , Cai Jie , Kumari Rajendra , Yin Yinfei 
Published: August 2019

BACKGROUND: Prostate cancer is one of the most common cancer worldwide with limited treatment options and very poor prognosis. Surgery, chemo therapy such as docetaxel (Taxotere®) and targeted therapies such as abiraterone (Zytiga®) and enzalutamide (Xtandi®) are the options available for prostate cancer patients but they all have their limitations. The development of new prostate cancer therapy has been slow due to the lack or preclinical models that adequately represent the spectrum of benign, latent, aggressive, and metastatic forms of the human disease. PDX have been reported to be more clinically relevant that cell lines but the generation of prostate PDX models has always been challenging. Here we report the establishment and validation of a panel of prostate PDX models and their utilization in preclinical studies which will help prostate cancer research.

MATERIAL & METHODS: Primary prostate cancer samples from patients undergoing radical prostatectomy in the UK were collected with ethical consent. These samples were then inoculated subcutaneously in Rag2-/-gC-/- mice (Jackson Laboratory) to generate PDX models. Subcutaneous tumor growth was evaluated and monitored by electronic callipers. Successfully established PDX tissue were collected for RNA sequencing and immunohistochemistry (IHC) for key prostate markers. PDX were also tested for sensitivity to docetaxel (Taxotere®), abiraterone and enzalutamide in vivo in mice bearing subcutaneous tumours. Tumours were samples pre and post dosing as well as blood samples collected.

RESULTS: A panel of prostate PDX models have been established and expanded. Two models were established using tumour tissue from patients diagnosed with castrate resistant prostate cancer (CRPC) and two models were from patients who showed hormone sensitivity. Histologically the structure of the original patient sample was retained in the PDX models. These models also showed high KLK3 (PSA) expression levels by RNA sequencing and IHC staining as well as androgen receptor expression. One of the CRPC models showed a TMPRSS-ETS fusion, response to docetaxel (p&lt;0.0001, Two way ANOVA) in vivo and poor response to abiraterone and enzalutamide, whereas the second CRPC model showed no response to any of the agents tested.

CONCLUSIONS: We have established and characterised a panel of prostate PDX models which provide unique and clinically relevant models for preclinical drug evaluation for prostate cancer.

Citation Format: Jason Davis, Anthony Oakden, Jane Wrigley, Chira Roberts, W Qian, Bin Fan, A Collins, Davy Ouyang, Jie Cai, Rajendra Kumari, Yinfei Yin. Establishment of a panel of prostate patient derived xenograft (PDX) models and evaluation of anti-androgen therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1060.