Abstract A009: Evaluation of hormonal therapy in a panel of prostate patient-derived xenograft models and comparison to standard cell line models

Abstract

Abstract Background: Prostate cancer is the second most common cancer worldwide for males, and the fourth most common cancer overall, with more than 1 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 that are routinely used. Methods: Prostate cancer samples obtained from patients undergoing surgery were collected with ethical consent, disaggregated, and established subcutaneously in Rag-2 knockout 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). Subcutaneous tumor growth of prostate models was evaluated 3 times a week by measuring the tumor in two dimensions using electronic calipers for the duration of the study, and tumor volumes were estimated. For orthotopic PC3M, tumor growth was checked once weekly by bioluminescent imaging (BLI). Briefly, the mice were injected (s.c.) with 150mg/kg D-Luciferin prior to imaging, anesthetized 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. 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. The tumor response to standard-of-care agents such as docetaxel, abiraterone, and enzalutamide will be reported. Conclusions: We have characterized both cell- and patient-derived prostate cancer xenograft models that will provide a clinically relevant platform spanning the different stages of the disease for preclinical drug evaluation. Citation Format: Nektaria Papadopoulou, Louise Woolley, Louise Wainwright, Lucy Harris, Jane Wrigley, Jason King, Anne Collins, Rajendra Kumari. Evaluation of hormonal therapy in a panel of prostate patient-derived xenograft models and comparison to standard cell line models [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A009.