Establishment and characterization of patient-derived xenografts for hormone-naïve and castrate-resistant prostate cancers to improve treatment modality evaluation

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 hormonenaïve (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.

The Essential Factors of Establishing Patient-derived Tumor Model

“…In Wu et al's research, Control group was subcutaneously implanted with the tissue without testosterone, whereas in the testosterone groups implantation was performed subcutaneously or under the renal capsule and testosterone was supplemented. As a result, mice supplemented with androgen displayed faster tumor growth than those in the control group [45]. Thus, during the establishment of PDX in hormone-dependent tumors, the addition of a certain amount of the corresponding hormone in mice will help to derive the tumor more efficiently.…”

LRRC8A Is a Promising Prognostic Biomarker and Therapeutic Target for Pancreatic Adenocarcinoma

“…PAAD tissues were obtained from the Department of Pathology of Xijing Hospital, and patient consent was reviewed and approved by the Xijing Hospital Clinical Research Ethics Board (certificate number KY2015432). Based on standard protocols [ 22 ], IHC analysis was performed using antibodies such as LRRC8A (Biobyt, Cambridge, United Kingdom; orb185053) and CD8 (Proteintech, Rosemont, IL, USA; 66868-1-Ig). The area of positive cells, average optical density values, and integrated optical density values were calculated using Image-Pro Plus analysis software 2020 to evaluate the immunohistochemical results.…”

Generation, evolution, interfering factors, applications, and challenges of patient-derived xenograft models in immunodeficient mice

“…In prostate cancer, the development of the prostate cancer xenograft model has been hampered by low success rates, in part by the poor vascularization of the transplantation site, which is successful only when applied to advanced cancers with high growth rates [ 47 ]. Supplementation of exogenous androgen shortened the latency of tumorigenesis and improved the rate of tumorigenesis [ 48 ]. Lin et al supplemented testosterone in non-obese diabetic (NOD)/SCID male mice, resulting in a 44% transplantation success rate [ 47 ].…”