Abstract A114: Characterization of a metastatic prostate cancer xenograft derived from a patient of African ancestry

Abstract

Abstract Background: Prostate cancer (PCa) is a clinically and molecularly heterogeneous disease, with differences in incidence and mortality among and between racial groups, which grade and stage only partially predict. Prostate cancer patient-derived xenografts (PCPDXs) are essential for studying PCa biology and testing new therapeutics in models that we expect to be reflective of the clinical setting. To date, PCPDXs have been difficult to establish due to lack of solid tumor content and poor uptake rates in mice. In the present study, we established and characterized the first PCPDX from a highly aggressive and metastatic tumor sample from a patient of African ancestry. Methods: We collected the PCa sample from the patient at the time of surgery after initiating stage-specific standard-of-care treatment. Tissue was minced and implanted into the kidney capsule of 8- to 10-week-old SCID mice. Once the explant was established, tissue was collected and formalin-fixed, paraffin-embedded for histologic evaluation. An initial section was stained using hematoxylin and eosin and another section was stained by PIN4 (p63, CKBE12, racemase) for immunohistochemical (IHC) analysis to confirm diagnosis of PCa. To obtain genetically estimated indicators of race, we performed ancestral genotyping. We evaluated response to chemical castration with 10mg/kg enzalutamide administered 5 days per week by oral gavage. Tumor growth was measured with calipers every day. Results: We established a PCPDX from a core prostate sample taken from a patient diagnosed with adenocarcinoma of the prostate (Gleason 10), metastatic to lymph nodes and penis undergoing a pelvic exenteration. Ancestral genotyping estimated 90% African ancestry. IHC staining showed this model to be highly tumorigenic and PSA negative. Passaged tumors took in 15 out of 15 SCID mice and reached 10mm3 within 3 weeks. This model does not show a significant decrease in growth in response to treatment with the androgen receptor inhibitor, enzalutamide. Further characterization using IHC, RNA and whole-exome sequencing, castration, drug treatment, and assays for metastatic potential are currently under way. Conclusions: Establishing this PCPDX provides a unique model of metastatic, androgen-independent PCa in a patient of African ancestry. Prior to this study, there had yet to be a PCPDX model derived from a patient of African ancestry. We established this PCPDX from a Gleason 10 PCa, supporting previous data of success in grafting this type of aggressive PCa into a mouse. It has a very high take rate and growth rate relative to other PCa models. Such a model will enable interrogation of PCa from a patient of African ancestry. Once a larger panel of PCPDXs from racially diverse patients is established, we will be able to achieve a more complete characterization of this disease and use such models to develop new biomarkers and therapeutic agents. Ultimately, these tools will improve outcomes for all men with aggressive PCa and reduce PCa disparities for patients of African ancestry. Citation Format: Brendon M. Patierno, Wayne Glover, Wen-Chi Foo, Jason A. Somarelli, Kathryn E. Ware, Lingfan Xu, Yanjing Li, Xufeng Chen, Daniel J. George, Rick A. Kittles, Andrew J. Armstrong, Shannon J. McCall, Jiaoti Huang, Jennifer A. Freedman, Steven R. Patierno, David S. Hsu. Characterization of a metastatic prostate cancer xenograft derived from a patient of African ancestry [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr A114.