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

Brendon M. Patierno, Wen Chi Foo, Tyler Allen, Jason A. Somarelli, Kathryn E. Ware, Santosh Gupta, Sandra Wise, John P. Wise, Xiaodi Qin, Dadong Zhang, Lingfan Xu, Yanjing Li, Xufeng Chen, Brant A. Inman, Shannon J. McCall, Jiaoti Huang, Rick A. Kittles, Kouros Owzar, Simon Gregory, Andrew J. ArmstrongDaniel J. George, Steven R. Patierno, David S. Hsu, Jennifer A. Freedman

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
JournalProstate Cancer and Prostatic Diseases
DOIs
StateAccepted/In press - 2021

ASJC Scopus subject areas

  • Oncology
  • Urology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Characterization of a castrate-resistant prostate cancer xenograft derived from a patient of West African ancestry'. Together they form a unique fingerprint.

Cite this