Abstract 1453: Development and evaluation of subcutaneous and orthotopic PC3M metastatic prostate cancer xenograft model in SRG rats for therapeutic assessment

Abstract

Abstract Introduction: Prostate cancer is the most prevalent cause of cancer deaths in American males after lung cancer. The establishment of clinically relevant prostate cancer models is crucial for advancing our understanding of the disease and evaluating potential therapeutics. Oncology studies in rats provide a secondary species to mice with the advantage of extensive longitudinal blood sampling and tumor biopsies in pharmacodynamics analysis. This in vivo study evaluates the behavior of subcutaneous and orthotopic luciferase (luc) tagged metastatic PC3M-luc cells in immunodeficient SRG rats (Hera Biolabs) for tumor growth kinetics, metastasis, and response to paclitaxel and carboplatin alone and in combination. Methods: PC3M-luc cells were implanted subcutaneously into the right flank or orthotopically into the prostate of SRG rats. Subcutaneous tumor progression and treatment responses were monitored using calipers and bioluminescent imaging (BLI), with the capacity to detect developing metastases prior to necropsy. Orthotopic implants were monitored exclusively using BLI. Tolerability was evaluated based on biweekly changes in body weight, daily observations for signs of tumor- or treatment-related clinical signs, necropsy results, and complete blood count (CBC) and clinical chemistry marker comparisons with immunocompetent CD rats. Results: PC3M-luc prostate carcinoma was successfully established orthotopically and subcutaneously in SRG rats, with similar growth rates and the development of spontaneous metastases to distant organs, modeling metastases observed in prostate cancer patients. Paclitaxel treatment was less tolerated in SRG rats in comparison to nude rats, enhanced toxicity was observed when combined with carboplatin. Comparison of CBC and clinical chemistry blood markers in naïve immunocompetent CD and immunodeficient SRG rats differed mainly in White Blood Cell (WBC) counts that were significantly lower in SRG rats, as expected due to the lack of mature B, T, and NK cells in these animals. Conclusion: The development of orthotopic and subcutaneous PC3M-luc prostate cancer models in rats provides a valuable alternative platform for assessing the effectiveness of established and novel therapies. This rat-based models offers a secondary species for comparison of prostate cancer behavior in mice, successfully mimics the clinical development of metastases, and provides additional insights into disease progression and therapeutic strategies. Future studies will focus on the assessment of tolerability and combination therapy strategies for improved treatment outcomes. Citation Format: Kyle Draheim, Elizabeth Rainbolt, Bincy John, Cara Clouse, Karyn Shinn, Justin Avery, Koh Meng Aw Yong, Chassidy Hall, Patrick Fadden, Anya Avrutskaya. Development and evaluation of subcutaneous and orthotopic PC3M metastatic prostate cancer xenograft model in SRG rats for therapeutic assessment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1453.