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

dc.contributor.author

Patierno, Brendon M

dc.contributor.author

Foo, Wen-Chi

dc.contributor.author

Allen, Tyler

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Somarelli, Jason A

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Ware, Kathryn E

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Gupta, Santosh

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Wise, Sandra

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Wise, John P

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Qin, Xiaodi

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Zhang, Dadong

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Xu, Lingfan

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Li, Yanjing

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Chen, Xufeng

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Inman, Brant A

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McCall, Shannon J

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Huang, Jiaoti

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Kittles, Rick A

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Owzar, Kouros

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Gregory, Simon

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Armstrong, Andrew J

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George, Daniel J

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Patierno, Steven R

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Hsu, David S

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Freedman, Jennifer A

dc.date.accessioned

2022-02-01T01:29:29Z

dc.date.available

2022-02-01T01:29:29Z

dc.date.issued

2021-10-13

dc.date.updated

2022-02-01T01:29:28Z

dc.description.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.
dc.identifier.issn

1365-7852

dc.identifier.issn

1476-5608

dc.identifier.uri

https://hdl.handle.net/10161/24270

dc.publisher

Springer Science and Business Media LLC

dc.relation.ispartof

Prostate cancer and prostatic diseases

dc.relation.isversionof

10.1038/s41391-021-00460-y

dc.title

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

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Conference

duke.contributor.orcid

Allen, Tyler|0000-0002-8729-6339

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Somarelli, Jason A|0000-0003-1510-9343

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Inman, Brant A|0000-0002-6060-4485

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McCall, Shannon J|0000-0003-3957-061X

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Huang, Jiaoti|0000-0003-1195-1998

duke.contributor.orcid

Gregory, Simon|0000-0002-7805-1743

duke.contributor.orcid

Armstrong, Andrew J|0000-0001-7012-1754

duke.contributor.orcid

Patierno, Steven R|0000-0003-0636-2128

pubs.issue

6

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Duke

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Nicholas School of the Environment

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School of Medicine

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Basic Science Departments

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Clinical Science Departments

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Institutes and Centers

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Biostatistics & Bioinformatics

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Molecular Genetics and Microbiology

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Pharmacology & Cancer Biology

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Family Medicine and Community Health

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Medicine

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Pathology

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Surgery

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Medicine, Medical Oncology

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Surgery, Surgical Sciences

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Surgery, Urology

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Duke Cancer Institute

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Marine Science and Conservation

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Duke Molecular Physiology Institute

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Neurology

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Neurology, MS & Neuroimmunology

pubs.publication-status

Published

pubs.volume

29

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