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Characterization of a castrate-resistant prostate cancer xenograft derived from a patient of West African ancestry



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.


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.


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.


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.

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Fig. 1: Patient clinical history.
Fig. 2: Patient and PDX immunohistochemical profiles.
Fig. 3: PCPDX DNA and RNA analysis.
Fig. 4: Response of the PCPDX and individual PCPDX tumors to clinically relevant doses of standard-of-care prostate cancer therapies.
Fig. 5: PCPDX gene expression post-treatment with enzalutamide, docetaxel, or cisplatin.
Fig. 6: H&E of mouse lung tissue with metastatic tumor foci.

Data availability

All RNA-sequencing data are available from GEO (GSE146402).


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We acknowledge the BioRepository & Precision Pathology Center (BRPC), a shared resource of the Duke University School of Medicine and Duke Cancer Institute, for providing access to the human biospecimens used under Institutional Review Board oversight in this work, the assistance of the Duke University Health System Clinical Molecular Diagnostics Laboratory, Duke Sequencing and Genomic Technologies Shared Resource, and the Duke Cancer Institute Bioinformatics Shared Resource, and Bonnie LaCroix, laboratory manager. Support: P30 Cancer Center Support Grant (P30 CA014236), NIH Basic Research in Cancer Health Disparities R01 Award R01CA220314 to SRP PI, JAF and DSH Co-I, DJG and KO Collaborator, WCF Pathologist.

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BMP: Conceptualization, Investigation, Formal Analysis, Writing, Visualization; WCF: Investigation, Formal Analysis, Writing, Visualization; TA: Formal Analysis, Writing, Visualization; JAS: Methodology, Writing; KEW: Methodology, Writing; SG: Investigation, Formal Analysis, Writing, Visualization; SW: Investigation, Formal Analysis, Writing, Visualization; JPW: Methodology, Writing; XQ: Formal Analysis, Writing, Visualization; DZ: Formal Analysis, Writing, Visualization; LX: Methodology; YL: Methodology; XC: Methodology; BAI: Conceptualization, Resources, Writing; SJM: Resources, Writing; JH: Conceptualization, Writing; RAK: Investigation, Formal Analysis, Writing, Visualization; KO: Conceptualization, Validation, Writing; SG: Conceptualization, Validation, Writing; AJA: Conceptualization, Writing; DJG: Conceptualization, Writing; SRP: Conceptualization, Writing, Supervision, Funding Acquisition; DSH: Conceptualization, Writing, Supervision, Project Administration, Funding Acquisition; JAF: Conceptualization, Writing, Supervision, Project Administration, Funding Acquisition.

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Correspondence to Jennifer A. Freedman.

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Patierno, B.M., Foo, WC., Allen, T. et al. Characterization of a castrate-resistant prostate cancer xenograft derived from a patient of West African ancestry. Prostate Cancer Prostatic Dis (2021).

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