Abstract B050: Reproducible and Effective Preclinical Models of Prostate Cancer Metastasis Established with PDXs

Abstract Metastatic castration resistant prostate cancer (mCRPC) is a lethal disease. Understanding the intricacy of this disease and developing targeted treatment is hampered by the lacking of clinically relevant animal models. LuCaP patient-derived xenografts (PDXs), established from advanced metastatic prostate cancer, are a large cohort that encompass the molecular and cellular heterogeneity of mCRPC. We have established four prostate cancer metastasis models from three androgen receptor (AR) positive lines (LuCaP136, LuCaP167 and LuCaP23.1) and one AR negative line LuCap145.2. The three AR positive LuCap lines metastasized to vertebrae and long bones with differing bone-associated histology while the AR negative LuCap145.2 metastasize to brain and spinal cord. The bone metastasis phenotypes of the models encompass: osteolytic (LuCaP136), mixed bone destruction and new bone formation (LuCaP167), and a highly osteoblastic histology (LuCaP23.1). LuCap136 and LuCap167 also metasize to soft tissues including adrenal, kidney and liver. Castration responses were studied on LuCap136 and LuCap167 models. Although both models are castration resistant, LuCap136 model initially are sensitive to castration with decreased tumor progression, and AR down-regulated in the metastatic sites. In contrast, tumor progression was not affected after castration in LuCap167 model. AR and ARV7 were up-regulated in metastatic cells. In summary, the LuCap PDX lines have the capacity for systemic growth in clinically accurate metastatic sites. In addition, the two AR positive models show different castration response which may be driven by different pathways. Understanding the complexity of these pathways would guide optimal selection of drug combinations to achieve the best outcome for patients with mCRPC. Citation Format: JuanJuan I. Yin, Asha Daryanani, Aian Alilin, Ross Lake, Kathy Kelly. Reproducible and effective preclinical models of prostate cancer metastasis established with PDXs [abstract]. In: Proceedings of the AACR Special Conference: Cancer Metastasis; 2022 Nov 14-17; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_2):Abstract nr B050.