A TRAMP-derived orthotopic prostate syngeneic (TOPS) cancer model for investigating anti-tumor treatments

Background: Patients with advanced prostate cancer have limited curative options, therefore new treatments are needed. Mouse models play a pivotal role in the discovery anddevelopment ofnewtreatments. In the present study, a TRAMP-derived Orthotopic Prostate Syngeneic (TOPS) mouse model was developed and found to provide a consistent means of monitoring tumor and metastatic responses to novel treatments. Methods: ThemouseTOPSmodelwasgenerated using luciferase transducedTRAMP- C2 prostate cancer cells that were orthotopically injected into Bl6 mice by ultrasound guidance. Tumor growth and development was monitored using ultrasound and bioluminescence imaging. Results: Tumors and metastases were consistently established and increases in tumor size correlated with increases in bioluminescence. In addition, when mice with an established tumor werecastrated, tumor progression mirrored clinical progression.We further treated the TOPS model with an oncolytic Herpes Simplex virus and showed thatwewere able to monitor the therapeutic effect of the orthotopic tumor after virus treatment through IVIS imaging system. Conclusion: We have developed a powerful animal model to advance the current selection of effective treatments for patients with advanced prostate cancer.