Abstract
Patient-derived xenografts (PDXs) are generated by engrafting human tumours into mice. Serially transplantable PDXs are used to study tumour biology and test therapeutics, linking the laboratory to the clinic. Although few prostate cancer PDXs are available in large repositories, over 330 prostate cancer PDXs have been established, spanning broad clinical stages, genotypes and phenotypes. Nevertheless, more PDXs are needed to reflect patient diversity, and to study new treatments and emerging mechanisms of resistance. We can maximize the use of PDXs by exchanging models and datasets, and by depositing PDXs into biorepositories, but we must address the impediments to accessing PDXs, such as institutional, ethical and legal agreements. Through collaboration, researchers will gain greater access to PDXs representing diverse features of prostate cancer.
| Original language | English |
|---|---|
| Pages (from-to) | 371-384 |
| Number of pages | 14 |
| Journal | Nature Reviews Urology |
| Volume | 20 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jun 2023 |
Bibliographical note
Funding Information:Most PDXs of prostate cancer have been generated by academic research laboratories, including laboratories that participated in the Movember GAP1 PDX project, and several groups have established sizeable cohorts of PDXs with diverse features. These cohorts are an important resource for the field of prostate cancer research, but a standardized system for sharing PDX resources has yet to be established. Three teams with collections of prostate cancer PDXs — University of Washington, Johns Hopkins University and Monash University — established a synergy consortium to test combination therapies for castration-resistant prostate cancer (CRPC), funded by the US Prostate Cancer Congressionally Directed Medical Research Program. As one aim of the programme was to identify opportunities to expand this collaboration, a series of virtual workshops involving laboratories with substantial collections of PDXs was organized in 2020 (Table ). During the workshops, an anonymous poll on PDX use and sharing was conducted to capture the views of 25 international researchers with expertise in prostate cancer PDXs (). ,,,–
Funding Information:
The authors thank the participants of the Virtual Prostate Cancer PDX Symposium series for sharing their views. They acknowledge the patients, clinical co-ordinators, clinicians and scientists who contribute to the establishment and maintenance of each of the collections of prostate cancer PDXs discussed in this Perspective. Authors from Monash University and the Peter MacCallum Cancer Centre thank members of the Melbourne Urological Research Alliance, kConFab, and CASCADE. Authors from the University of Washington/Fred Hutchinson Cancer Research Center would like to thank the patients who generously donated the tissue that made this research possible. The authors also thank J. Conner, M. Dalos, D. Sondheim and the Comparative Medicine Animal Caregivers for assistance with the LuCaP xenograft work. Additionally, they thank P. Lange, R. Vessella, F. Vakar-Lopez, M. Roudier, X. Zhang, B. Nghiem and the rapid autopsy teams and physicians in the Urology and Medical Oncology Departments at the University of Washington. The authors receive funding from the Movember Foundation Global Action Plan 1 PDX Project; US Department of Defense through the Prostate Cancer Research Program (W81XWH1810347, W81XWH1810348 and W81XWH1810349; opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the Department of Defense); the Movember Foundation (Global Action Plan 1); the Victorian Cancer Agency (MCRF15023, MCRF18017 and MCRF17005; CAPTIV Program); the National Health and Medical Research Council, Australia (1102752, 1138242, 1140222, 1156570, 1185616, 2011033 and 2011391); the Rotary Club of Manningham; RULE Prostate Cancer and the EJ Whitten Foundation; the Peter and Lyndy White Foundation; TissuPath Pathology; the Peter MacCallum Cancer Foundation; the Pacific Northwest Prostate Cancer SPORE (P50CA97186); the Department of Defense Prostate Cancer Biorepository Network (W81XWH-14-2-0183); CDMRP award W81XWH-21-1-0264; National Institute of Health/National Cancer Institute (P01 CA163227, R01CA234715, U01 CA224044-03, U54 CA233223, SBIR Phase I HHSN26120700015C); the Baylor College of Medicine, Minority PDX Development and Trial Center: Baylor College of Medicine and MD Anderson Cancer Center Collaboration on Mechanistic Studies to Dissect and Combat Health Disparities in Cancer, SBIR Phase II/Mimetas US, Inc); the Prostate Cancer Foundation; the Institute for Prostate Cancer Research; the Richard M. Lucas Foundation; the Craig Watjen Memorial Fund; Fond’Action contre le cancer (Young Investigator Award 2020); the Department of Surgery of the University Hospital Basel; the David H. Koch Center for Applied Research in Genitourinary Cancers at MD Anderson; the Canadian Institutes of Health Research (141635, 144159, 153081 and 173338); the Terry Fox Research Institute (1062); the Mitacs Accelerate Program (IT10125, IT06414, IT12387 and IT14958); and the EU Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant (721746; ‘TRANSPOT’).
Funding Information:
The authors thank the participants of the Virtual Prostate Cancer PDX Symposium series for sharing their views. They acknowledge the patients, clinical co-ordinators, clinicians and scientists who contribute to the establishment and maintenance of each of the collections of prostate cancer PDXs discussed in this Perspective. Authors from Monash University and the Peter MacCallum Cancer Centre thank members of the Melbourne Urological Research Alliance, kConFab, and CASCADE. Authors from the University of Washington/Fred Hutchinson Cancer Research Center would like to thank the patients who generously donated the tissue that made this research possible. The authors also thank J. Conner, M. Dalos, D. Sondheim and the Comparative Medicine Animal Caregivers for assistance with the LuCaP xenograft work. Additionally, they thank P. Lange, R. Vessella, F. Vakar-Lopez, M. Roudier, X. Zhang, B. Nghiem and the rapid autopsy teams and physicians in the Urology and Medical Oncology Departments at the University of Washington. The authors receive funding from the Movember Foundation Global Action Plan 1 PDX Project; US Department of Defense through the Prostate Cancer Research Program (W81XWH1810347, W81XWH1810348 and W81XWH1810349; opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the Department of Defense); the Movember Foundation (Global Action Plan 1); the Victorian Cancer Agency (MCRF15023, MCRF18017 and MCRF17005; CAPTIV Program); the National Health and Medical Research Council, Australia (1102752, 1138242, 1140222, 1156570, 1185616, 2011033 and 2011391); the Rotary Club of Manningham; RULE Prostate Cancer and the EJ Whitten Foundation; the Peter and Lyndy White Foundation; TissuPath Pathology; the Peter MacCallum Cancer Foundation; the Pacific Northwest Prostate Cancer SPORE (P50CA97186); the Department of Defense Prostate Cancer Biorepository Network (W81XWH-14-2-0183); CDMRP award W81XWH-21-1-0264; National Institute of Health/National Cancer Institute (P01 CA163227, R01CA234715, U01 CA224044-03, U54 CA233223, SBIR Phase I HHSN26120700015C); the Baylor College of Medicine, Minority PDX Development and Trial Center: Baylor College of Medicine and MD Anderson Cancer Center Collaboration on Mechanistic Studies to Dissect and Combat Health Disparities in Cancer, SBIR Phase II/Mimetas US, Inc); the Prostate Cancer Foundation; the Institute for Prostate Cancer Research; the Richard M. Lucas Foundation; the Craig Watjen Memorial Fund; Fond’Action contre le cancer (Young Investigator Award 2020); the Department of Surgery of the University Hospital Basel; the David H. Koch Center for Applied Research in Genitourinary Cancers at MD Anderson; the Canadian Institutes of Health Research (141635, 144159, 153081 and 173338); the Terry Fox Research Institute (1062); the Mitacs Accelerate Program (IT10125, IT06414, IT12387 and IT14958); and the EU Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant (721746; ‘TRANSPOT’).
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