Movember GAP1 PDX project: An international collection of serially transplantable prostate cancer patient-derived xenograft (PDX) models

Movember GAP1 PDX 项目:可连续移植的前列腺癌患者来源异种移植 (PDX) 模型的国际集合

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作者:Nora M Navone, Wytske M van Weerden, Robert L Vessella, Elizabeth D Williams, Yuzhuo Wang, John T Isaacs, Holly M Nguyen, Zoran Culig, Gabri van der Pluijm, Cyril A Rentsch, Rute B Marques, Corrina M A de Ridder, Lukas Bubendorf, George N Thalmann, William Nathaniel Brennen, Frédéric R Santer, Patri

Background

While it has been challenging to establish prostate cancer patient-derived xenografts (PDXs), with a take rate of 10-40% and long latency time, multiple groups throughout the world have developed

Conclusion

Our results demonstrate the clinical relevance of this series of PDXs as a platform for both basic science studies and therapeutic discovery/drug development. The present report provides the prostate cancer community with a summary of the basic characteristics and a contact information for collaborations using these models.

Methods

PDX models were established in immunocompromised mice via subcutaneous or subrenal-capsule implantation. Dual-label species (ie, human vs mouse) specific centromere and telomere Fluorescence In Situ Hybridization (FISH) and immuno-histochemical (IHC) staining of tissue microarrays (TMAs) containing replicates of the PDX models were used for characterization of expression of a number of phenotypic markers important for prostate cancer including AR (assessed by IHC and FISH), Ki67, vimentin, RB1, P-Akt, chromogranin A (CgA), p53, ERG, PTEN, PSMA, and epithelial cytokeratins.

Results

Within this series of PDX models, the full spectrum of clinical disease stages is represented, including androgen-sensitive and castration-resistant primary and metastatic prostate adenocarcinomas as well as prostate carcinomas with neuroendocrine differentiation. The annotated clinical characteristics of these PDXs were correlated with their marker expression profile.

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