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

Publication ,  Conference
Patierno, BM; Foo, W-C; Allen, T; Somarelli, JA; Ware, KE; Gupta, S; Wise, S; Wise, JP; Qin, X; Zhang, D; Xu, L; Li, Y; Chen, X; Inman, BA ...
Published in: Prostate Cancer Prostatic Dis
September 2022

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.

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Published In

Prostate Cancer Prostatic Dis

DOI

EISSN

1476-5608

Publication Date

September 2022

Volume

25

Issue

3

Start / End Page

513 / 523

Location

England

Related Subject Headings

  • Urology & Nephrology
  • Prostatic Neoplasms, Castration-Resistant
  • Prostatic Neoplasms
  • Orchiectomy
  • Mice
  • Male
  • Humans
  • Heterografts
  • Docetaxel
  • Black or African American
 

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Patierno, B. M., Foo, W.-C., Allen, T., Somarelli, J. A., Ware, K. E., Gupta, S., … Freedman, J. A. (2022). Characterization of a castrate-resistant prostate cancer xenograft derived from a patient of West African ancestry. In Prostate Cancer Prostatic Dis (Vol. 25, pp. 513–523). England. https://doi.org/10.1038/s41391-021-00460-y
Patierno, Brendon M., Wen-Chi Foo, Tyler Allen, Jason A. Somarelli, Kathryn E. Ware, Santosh Gupta, Sandra Wise, et al. “Characterization of a castrate-resistant prostate cancer xenograft derived from a patient of West African ancestry.” In Prostate Cancer Prostatic Dis, 25:513–23, 2022. https://doi.org/10.1038/s41391-021-00460-y.
Patierno BM, Foo W-C, Allen T, Somarelli JA, Ware KE, Gupta S, et al. Characterization of a castrate-resistant prostate cancer xenograft derived from a patient of West African ancestry. In: Prostate Cancer Prostatic Dis. 2022. p. 513–23.
Patierno, Brendon M., et al. “Characterization of a castrate-resistant prostate cancer xenograft derived from a patient of West African ancestry.Prostate Cancer Prostatic Dis, vol. 25, no. 3, 2022, pp. 513–23. Pubmed, doi:10.1038/s41391-021-00460-y.
Patierno BM, Foo W-C, Allen T, Somarelli JA, Ware KE, Gupta S, Wise S, Wise JP, Qin X, Zhang D, Xu L, Li Y, Chen X, Inman BA, McCall SJ, Huang J, Kittles RA, Owzar K, Gregory S, Armstrong AJ, George DJ, Patierno SR, Hsu DS, Freedman JA. Characterization of a castrate-resistant prostate cancer xenograft derived from a patient of West African ancestry. Prostate Cancer Prostatic Dis. 2022. p. 513–523.

Published In

Prostate Cancer Prostatic Dis

DOI

EISSN

1476-5608

Publication Date

September 2022

Volume

25

Issue

3

Start / End Page

513 / 523

Location

England

Related Subject Headings

  • Urology & Nephrology
  • Prostatic Neoplasms, Castration-Resistant
  • Prostatic Neoplasms
  • Orchiectomy
  • Mice
  • Male
  • Humans
  • Heterografts
  • Docetaxel
  • Black or African American