Patient-Derived Prostate Cancer Models: PDXs, Organoids, and Others

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Motility and Adhesion".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 5766

Special Issue Editors


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Guest Editor
Professor Department of Urologic Sciences, UBC, Vancouver, BC, Canada
Interests: cancer biology; tumor dormancy; cancer modelling

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Guest Editor
Senior Lecturer and Research Director, Department of Life, Health and Chemical Sciences, Open University, Milton Keynes, UK
Interests: cancer; epigenetics; ncRNAs; cancer modeling
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Vancouver Prostate Centre, Vancouver, BC, Canada
Interests: prostate cancer; pathology; cancer modelling; therapeutic target discovery

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Guest Editor
1. Monash Partners Comprehensive Cancer Consortium, Monash Biomedicine Discovery Institute Cancer Program, Prostate Cancer Research Group, Department of Anatomy and Developmental Biology, Monash University, Clayton, Melbourne 3800, Australia
2. Peter MacCallum Cancer Centre, Victorian Comprehensive Cancer Centre (VCCC), Melbourne, VIC 3000, Australia
Interests: prostate cancer; endocrinology; steroid hormone action; men’s health; urology

Special Issue Information

Dear Colleagues,

We are delighted to invite you to contribute to a Cells Special Issue, “Patient-Derived Prostate Cancer Models: PDXs, Organoids, and Others.”

Prostate cancer remains one of the most common causes of cancer-related mortality in the world. Patient-derived prostate cancer models that closely represent the patients’ tumor are necessary for cancer discovery, anti-cancer drug development, and personalized cancer therapy. Research in the prostate cancer field is hampered by the limited number of human cell lines and xenograft models, However, during the last few decades, many advances in Patient-derived prostate cancer models, e.g., patient-derived xenograft (PDX), organoid, and other models are addressing the critical need. We will make an effort to attract the top modellers in the field to contribute to this Special Issue in the hope that this special collection will serve as the most informed resource for researchers and clinicians dealing with, or interested in, the use of Patient-derived prostate cancer models in cancer research. We expect that this Special Issue will propagate innovative concepts and prompt the development of ground-breaking technological solutions in the field.

We are looking forward to your contributions to this Special Issue.

Prof. Dr. Yuzhuo Wang, Ph.D, FCAHS
Prof. Dr. Francesco Crea
Prof. Dr. Dong Lin 
Prof. Dr. Gail Risbridger
Guest Editors

Manuscript Submission Information

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Keywords

  • Prostate cancer
  • Patient-derived models
  • Patient-derived xenograft (PDX)
  • Primary culture
  • Organoids
  • 2D-conditionally programmed model

Published Papers (2 papers)

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Research

21 pages, 5876 KiB  
Article
Patient-Derived Xenografts and Organoids Recapitulate Castration-Resistant Prostate Cancer with Sustained Androgen Receptor Signaling
by Annelies Van Hemelryk, Ingrid Tomljanovic, Corrina M. A. de Ridder, Debra C. Stuurman, Wilma J. Teubel, Sigrun Erkens-Schulze, Esther I. Verhoef, Sebastiaan Remmers, Amrish J. Mahes, Geert J. L. H. van Leenders, Martin E. van Royen, Harmen J. G. van de Werken, Magda Grudniewska, Guido W. Jenster and Wytske M. van Weerden
Cells 2022, 11(22), 3632; https://doi.org/10.3390/cells11223632 - 16 Nov 2022
Cited by 6 | Viewed by 2819
Abstract
Castration-resistant prostate cancer (CRPC) remains an incurable and lethal malignancy. The development of new CRPC treatment strategies is strongly impeded by the scarcity of representative, scalable and transferable preclinical models of advanced, androgen receptor (AR)-driven CRPC. Here, we present contemporary patient-derived xenografts (PDXs) [...] Read more.
Castration-resistant prostate cancer (CRPC) remains an incurable and lethal malignancy. The development of new CRPC treatment strategies is strongly impeded by the scarcity of representative, scalable and transferable preclinical models of advanced, androgen receptor (AR)-driven CRPC. Here, we present contemporary patient-derived xenografts (PDXs) and matching PDX-derived organoids (PDXOs) from CRPC patients who had undergone multiple lines of treatment. These models were comprehensively profiled at the morphologic, genomic (n = 8) and transcriptomic levels (n = 81). All are high-grade adenocarcinomas that exhibit copy number alterations and transcriptomic features representative of CRPC patient cohorts. We identified losses of PTEN and RB1, MYC amplifications, as well as genomic alterations in TP53 and in members of clinically actionable pathways such as AR, PI3K and DNA repair pathways. Importantly, the clinically observed continued reliance of CRPC tumors on AR signaling is preserved across the entire set of models, with AR amplification identified in four PDXs. We demonstrate that PDXs and PDXOs faithfully reflect donor tumors and mimic matching patient drug responses. In particular, our models predicted patient responses to subsequent treatments and captured sensitivities to previously received therapies. Collectively, these PDX-PDXO pairs constitute a reliable new resource for in-depth studies of treatment-induced, AR-driven resistance mechanisms. Moreover, PDXOs can be leveraged for large-scale tumor-specific drug response profiling critical for accelerating therapeutic advances in CRPC. Full article
(This article belongs to the Special Issue Patient-Derived Prostate Cancer Models: PDXs, Organoids, and Others)
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18 pages, 2709 KiB  
Article
Framework of Intrinsic Immune Landscape of Dormant Prostate Cancer
by Nelson K. Y. Wong, Xin Dong, Yen-Yi Lin, Hui Xue, Rebecca Wu, Dong Lin, Colin Collins and Yuzhuo Wang
Cells 2022, 11(9), 1550; https://doi.org/10.3390/cells11091550 - 05 May 2022
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Abstract
Androgen deprivation therapy (ADT) is the standard therapy for men with advanced prostate cancer (PCa). PCa often responds to ADT and enters a dormancy period, which can be recognized clinically as a minimal residual disease. However, the majority of these patients will eventually [...] Read more.
Androgen deprivation therapy (ADT) is the standard therapy for men with advanced prostate cancer (PCa). PCa often responds to ADT and enters a dormancy period, which can be recognized clinically as a minimal residual disease. However, the majority of these patients will eventually experience a relapse in the form of castration-resistant PCa with poor survival. Therefore, ADT-induced dormancy is a unique time window for treatment that can provide a cure. The study of this well-recognized phase of prostate cancer progression is largely hindered by the scarcity of appropriate clinical tissue and clinically relevant preclinical models. Here, we report the utility of unique and clinically relevant patient-derived xenograft models in the study of the intrinsic immune landscape of dormant PCa. Using data from RNA sequencing, we have reconstructed the immune evasion mechanisms that can be utilized by dormant PCa cells. Since dormant PCa cells need to evade the host immune surveillance for survival, our results provide a framework for further study and for devising immunomodulatory mechanisms that can eliminate dormant PCa cells. Full article
(This article belongs to the Special Issue Patient-Derived Prostate Cancer Models: PDXs, Organoids, and Others)
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