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

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.

Department

Description

Provenance

Subjects

Citation

Published Version (Please cite this version)

10.1038/s41391-021-00460-y

Scholars@Duke

Foo

Wen Chi Foo

Associate Professor of Pathology
Allen

Tyler Allen

Research Program Leader, Tier 1
Somarelli

Jason Andrew Somarelli

Assistant Professor in Medicine
McCall

Shannon Jones McCall

Associate Professor of Pathology

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.

Huang

Jiaoti Huang

The Johnston-West Endowed Department Chair of Pathology

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.

Owzar

Kouros Owzar

Professor of Biostatistics & Bioinformatics

cancer pharmacogenomics
drug induced neuropathy, neutropenia and hypertension
statistical genetics
statistical methods for high-dimensional data
copulas
survival analysis
statistical computing

Patierno

Steven Patierno

Charles D. Watts Distinguished Professor of Medicine

Patierno's current translational research interests are focused on the genomics molecular biology of cancer disparities, cancer biology, molecular pharmacology and targeted experimental therapeutics to control prostate, breast and lung tumor aggressiveness. He is an internationally recognized expert in cancer control, cancer causation and molecular carcinogenesis, which includes a broad spectrum of laboratory and population level research.   Patierno is also actively engaged in cancer health disparities and healthcare delivery research focused on patient navigation, survivorship, community-based interventions, mHealth, implementation sciences, cancer care economics, and policy.

Freedman

Jennifer Freedman

Associate Professor in Medicine

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