Abstract B080: A patient-derived metastasis model with spontaneous neuroendocrine transformation

Abstract Background: Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease, in which patients each carry distinct molecular features that drive metastatic progression. However, the lack of clinically representative models that recapitulate this disease have limited our understanding in the heterogeneity between patients. LuCaP 147, established from a liver metastasis biopsy, is a prostate cancer transplantable xenograft carrying AR and SPOP mutations with a further hypermutated phenotype, as well as loss of MSH2 and MSH6 expression. Methods: Using LuCaP 147, we developed a novel patient-derived metastasis (PDM) model in NSG mice via intracardiac injection. The development of metastasis was monitored through weekly bioluminescent imaging. We analyzed the tumor burden and survival rate of the PDM147 models. At the endpoint, long bones, spines and soft tissues were collected. To evaluate the histologic phenotype of PDM147, tissue sections were stained by immunohistochemistry (IHC) for adenocarcinoma markers including AR and neuroendocrine markers (which include SOX2, ASCL1, and SYP). Results: After intracardiac injection, tumor burden (BLI) was detected after 5 weeks, and mice developed morbidity after 7-8 weeks. H 2026 Jan 20-22; Philadelphia PA. Philadelphia (PA): AACR; Cancer Res 2026;86 (2Suppl): Abstract nr B080.