Research Paper Volume 12, Issue 4 pp 3848—3861
Establishment and characterization of patient-derived xenografts for hormone-naïve and castrate-resistant prostate cancers to improve treatment modality evaluation
- 1 Division of Cancer Biology, Laboratory Animal Center, The Fourth Military Medical University, Xi’an, Shaanxi 710032, China
- 2 Biomedicine Application Laboratory, School of Life Science and Technology, Xidian University, Xi’an, Shaanxi 710071, China
- 3 Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi 710032, China
Received: November 3, 2019 Accepted: January 28, 2020 Published: February 24, 2020
https://doi.org/10.18632/aging.102854How to Cite
Copyright © 2020 Wu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Prostate cancer (PC) is a heterogeneous disease characterized by variable morphological patterns. Thus, establishing a patient-derived xenograft (PDX) model that retains the key features of the primary tumor for each type of PC is important for appropriate evaluation. In this study, we established PDX models of hormone-naïve (D17225) and castration-resistant (B45354) PC by implanting fresh tumor samples, obtained from patients with advanced PC under the renal capsule of immune-compromised mice. Supplementation with exogenous androgens shortened the latent period of tumorigenesis and increased the tumor formation rate. The PDX models exhibited the same major genomic and phenotypic features of the disease in humans and maintained the main pathological features of the primary tumors. Moreover, both PDX models showed different outcomes after castration or docetaxel treatment. The hormone-naïve D17225 PDX model displayed a range of responses from complete tumor regression to overt tumor progression, and the development of castrate-resistant PC was induced after castration. The responses of the two PDX models to androgen deprivation and docetaxel were similar to those observed in patients with advanced PC. These new preclinical PC models will facilitate research on the mechanisms underlying treatment response and resistance.