Abstract 1061: Animal models of prostate cancer

Background: Prostate cancer is the most common male malignancy and the second most common cause of cancer-related deaths in the United Kingdom and the United States. It’s a heterogeneous disease caused by different genetic mutations where the majority of prostate cancers are indolent and slow growing. However, some tumours are aggressive with the ability to invade local structures and metastasise leading to poor clinical outcome. One of the most important aspects in anti-cancer drug development is the availability of robust preclinical models which allow the efficacy of novel therapies to be examined. We have developed a reproducible, well growing and robust subcutaneous model of LNCaP with an effective response to both conventional standard of care (SOC) chemotherapy and androgen receptor inhibitors. Materials and Methods: Cells were subcutaneously implanted on the flank of NSG mice and treated with an anti-androgen with or without conventional chemotherapy starting after 15-20 days when the mean tumour volume was 150-200mm3. Animal weight and tumour volume was measured 3x weekly. Androgen receptor (AR) expression was analysed with immunohistochemistry and gene expression analysis before and after treatment. Results: The LNCaP cell line grew well in vivo with 100% take rate. Vehicle treated tumours doubled in size over the first 6 days of treatment and were 4.5x the mean starting volume by day 17 post-treatment start, when the group was removed from the study. Significant tumour growth inhibition was observed in response to both conventional and anti-androgen receptor treatment consistent with the maintained AR expression confirmed by gene expression analysis. Conclusion: This high take rate responsive model represents a significant improvement in subcutaneous xenograft models of prostate cancer, and allows the comparison of AR responsive therapies, alone or in combination with conventional SOC or irradiation. Current protocols employing luciferase transfected cells has also enabled evaluation of metastatic disease. Citation Format: Frida Ponthan, Matthew Brown, Emma Playle, Catherine Booth. Animal models of prostate cancer [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 1061.