Abstract 2824: Validation of a panel of patient-derived xenograft models for prostate caner and cell line models for preclinical drug evaluation

Abstract

Abstract Background: Prostate cancer is the second most common cancer worldwide for males, and the fourth most common cancer overall, with more than a million new cases diagnosed. However, progress toward understanding the biology of prostate cancer and the development of new therapies has been hampered by the lack of in vivo models that adequately represent the spectrum of benign, latent, aggressive, and metastatic forms of the human disease. Here we report the validation of a panel of patient-derived xenograft (PDX) models and their utilization in preclinical studies alongside cell line models of prostate cancer. Methods: Prostate cancer samples obtained from patients undergoing surgery were collected with ethical consent, disaggregated and established subcutaneously in Rag2-/-γC-/- mice (The Jackson Laboratory) to generate PDX models. Tumor material was diagnosed on the basis of operative histology and immunohistochemistry (IHC for PSA, androgen receptor expression). Tumor growth in both Rag2-/-γC-/- and NSG mice was evaluated in comparison to cell line models such LNCaP and PC3M. Briefly tumours were measured 3 times a week and tumour volumes were estimated using the formula 0.5 (LxW2) by measuring the tumour in two dimensions using electronic callipers for the duration of the study. For orthotopic PC3M, tumour growth was checked once weekly by bioluminescent imaging (BLI). Briefly, the mice were injected (s.c.) with 150mg/kg D-Luciferin prior to imaging, anaesthetised following administration of D-Luciferin and placed into the imaging chamber (Spectrum CT) and imaged for luminescence (ventral view). Results: We have established a bank of transplantable prostate cancer PDX and stocks are maintained in liquid nitrogen which can be resuscitated in in both Rag2-/-γC-/- and NSG mice. Two models were reported to be hormone sensitive and 2 models represented castrate resistant prostate cancer (CRPC) one of which has a TMPRSS-ETS fusion. In comparison cell-derived LNCaP requires testosterone to grow whereas the bioluminescent PC3M CRPC orthotopic model develops metastasis in the liver, lungs, lumbar lymph nodes, fore limbs and hind limbs representing the late stage of cancer. Conclusions: We have characterised both cell and patient-derived prostate cancer xenograft models which will provide a clinically relevant platform spanning the different stages of the disease for preclinical drug evaluation. Citation Format: Nektaria Papadopoulou, Jane Wrigley, Andrew McKenzie, Jason King, Louise Wainwright, Kelly Jones, Anne Collins, Rajendra Kumari. Validation of a panel of patient-derived xenograft models for prostate caner and cell line models for preclinical drug evaluation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2824. doi:10.1158/1538-7445.AM2017-2824