Abstract 4182: Development and evaluation of orthotopically and subcutaneously implanted luciferase-labeled prostate cancer xenograft models for therapeutic assessment

Abstract

Abstract Introduction: Prostate cancer is the most common male-specific cancer in many western countries including the US and the second 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 therapeutic interventions. In this in vivo project we characterize the tumor growth and response to therapy of two luciferase (luc) tagged human prostate cancer xenograft models of metastatic PC3M and non-metastatic DU145 cell lines. These models aim to replicate the variable clinical behavior of prostate cancer to provide valuable pre-clinical platforms to test existing and novel therapies. As a first step, these studies evaluate the effect of standard of care cytotoxic agents paclitaxel and carboplatin and the newer AXL kinase inhibitor bemcentinib alone and in combination on tumor growth kinetics and agent tolerability. Methods: PC3M-luc and DU145-luc cells were implanted subcutaneously on right flank or orthotopically into the prostate of NCG triple immunodeficient mice (Charles River). 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. Results: Orthotopic and subcutaneous implants of PC3M-luc demonstrated spontaneous metastasis to lungs and bones, replicating the established behavior of this cell line and effectively modeling metastases observed in prostate cancer patients. In contrast, orthotopic and subcutaneous implants of DU145-luc model did not metastasize. Both PC3M-luc and DU145-luc models independent of the tumor implant placement responded to paclitaxel treatment, with enhanced effects observed when combined with carboplatin. Notably, bemcentinib exhibited no activity as a single agent but showed promise when used in combination with cytotoxic agents. Conclusion: The development of orthotopic and subcutaneous PC3M-luc and DU145-luc prostate cancer models provides a valuable platform for assessing the effectiveness of established and novel therapies. These models mimic various clinical presentations of prostate cancer and promise to offer insights into disease progression and therapeutic strategies. Future studies will focus on durable responses and the assessment of other combination therapies for improved treatment outcomes. Citation Format: Kyle Draheim, Elizabeth Rainbolt, Bincy John, Cara Clouse, Andrew Wong, Brooke Wolff, Justin Avery, Chassidy Hall, Patrick Fadden, Anya Avrutskaya. Development and evaluation of orthotopically and subcutaneously implanted luciferase-labeled prostate cancer xenograft models 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 4182.