Characterization of a castrate-resistant prostate cancer xenograft derived from a patient of West African ancestry.
Date
2021-10-13
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Abstract
Background
Prostate cancer is a clinically and molecularly heterogeneous disease, with highest incidence and mortality among men of African ancestry. To date, prostate cancer patient-derived xenograft (PCPDX) models to study this disease have been difficult to establish because of limited specimen availability and poor uptake rates in immunodeficient mice. Ancestrally diverse PCPDXs are even more rare, and only six PCPDXs from self-identified African American patients from one institution were recently made available.Methods
In the present study, we established a PCPDX from prostate cancer tissue from a patient of estimated 90% West African ancestry with metastatic castration resistant disease, and characterized this model's pathology, karyotype, hotspot mutations, copy number, gene fusions, gene expression, growth rate in normal and castrated mice, therapeutic response, and experimental metastasis.Results
This PCPDX has a mutation in TP53 and loss of PTEN and RB1. We have documented a 100% take rate in mice after thawing the PCPDX tumor from frozen stock. The PCPDX is castrate- and docetaxel-resistant and cisplatin-sensitive, and has gene expression patterns associated with such drug responses. After tail vein injection, the PCPDX tumor cells can colonize the lungs of mice.Conclusion
This PCPDX, along with others that are established and characterized, will be useful pre-clinically for studying the heterogeneity of prostate cancer biology and testing new therapeutics in models expected to be reflective of the clinical setting.Type
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Scholars@Duke

Wen Chi Foo

Tyler Allen

Jason Andrew Somarelli

Shannon Jones McCall
As Vice Chair for Translational Research in the Department of Pathology, I am involved in numerous translational cancer research projects that rely on the study of human biological samples. I am the director of the Duke BioRepository & Precision Pathology Center (Duke BRPC), a shared resource of the School of Medicine and the Duke Cancer Institute. I serve as the PI for the National Cancer Institute's Cooperative Human Tissue Network Southern Division (a five-year UM1 grant), which lives in the Duke BRPC. My own area of research interest is gastrointestinal tract metaplasias and their relationship to carcinogenesis, particularly in the upper GI tract.

Jiaoti Huang
I am a physician-scientist with clinical expertise in the pathologic diagnosis of genitourinary tumors including tumors of the prostate, bladder, kidney and testis. Another area of interest is gynecologic tumors. In my research laboratory we study prostate cancer, focusing on molecular mechanisms of carcinogenesis and tumor progression, as well as biomarkers, imaging and novel therapeutic strategies. In addition to patient care and research, I am also passionate about education. I have trained numerous residents, fellows, graduate students and postdocs.

Jennifer Freedman
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