@article{86358ec3e5464d36adf7fe6fbceb8070,
title = "The MURAL collection of prostate cancer patient-derived xenografts enables discovery through preclinical models of uro-oncology",
abstract = "Preclinical testing is a crucial step in evaluating cancer therapeutics. We aimed to establish a significant resource of patient-derived xenografts (PDXs) of prostate cancer for rapid and systematic evaluation of candidate therapies. The PDX collection comprises 59 tumors collected from 30 patients between 2012–2020, coinciding with availability of abiraterone and enzalutamide. The PDXs represent the clinico-pathological and genomic spectrum of prostate cancer, from treatment-na{\"i}ve primary tumors to castration-resistant metastases. Inter- and intra-tumor heterogeneity in adenocarcinoma and neuroendocrine phenotypes is evident from bulk and single-cell RNA sequencing data. Organoids can be cultured from PDXs, providing further capabilities for preclinical studies. Using a 1 x 1 x 1 design, we rapidly identify tumors with exceptional responses to combination treatments. To govern the distribution of PDXs, we formed the Melbourne Urological Research Alliance (MURAL). This PDX collection is a substantial resource, expanding the capacity to test and prioritize effective treatments for prospective clinical trials in prostate cancer.",
author = "Risbridger, {Gail P.} and Clark, {Ashlee K.} and Porter, {Laura H.} and Roxanne Toivanen and Andrew Bakshi and Lister, {Natalie L.} and David Pook and Pezaro, {Carmel J.} and Shahneen Sandhu and Shivakumar Keerthikumar and {Quezada Urban}, Rosalia and Melissa Papargiris and Jenna Kraska and Madsen, {Heather B.} and Hong Wang and Richards, {Michelle G.} and Birunthi Niranjan and Samantha O{\textquoteright}Dea and Linda Teng and William Wheelahan and Zhuoer Li and Nicholas Choo and Ouyang, {John F.} and Heather Thorne and Lisa Devereux and Hicks, {Rodney J.} and Shomik Sengupta and Laurence Harewood and Mahesh Iddawala and Azad, {Arun A.} and Jeremy Goad and Jeremy Grummet and John Kourambas and Kwan, {Edmond M.} and Daniel Moon and Murphy, {Declan G.} and John Pedersen and David Clouston and Sam Norden and Andrew Ryan and Luc Furic and Goode, {David L.} and Mark Frydenberg and Lawrence, {Mitchell G.} and Taylor, {Renea A.}",
note = "Funding Information: G.P.R., R Taylor and M.G.L. (Research collaborations: Pfizer, Astellas, Zenith Epigenetics; non-financial); A.A.A. (Speakers Bureau: Astellas, Janssen, Novartis, Amgen, Ipsen, Bristol Myers Squibb; Merck Serono, Bayer; Honoraria: Astellas, Novartis, Sanofi, AstraZeneca, Tolmar, Telix, Merck Serono, Janssen, Bristol Myers Squibb, Ipsen, Bayer, Pfizer, Amgen, Noxopharm, Merck Sharpe Dome; Scientific Advisory Board: Astellas, Novartis, Sanofi, AstraZeneca, Tolmar, Pfizer, Telix, Merck Serono, Janssen, Bristol Myers Squibb, Ipsen, Bayer, Merck Sharpe Dome, Amgen, Noxopharm; Travel + Accommodation: Astellas, Merck Ser-ono, Amgen, Novartis, Janssen, Tolmar, Pfizer; Investigator Research Funding: Astellas, Merck Serono, AstraZeneca; Institutional Research Funding: Bristol Myers Squibb, AstraZeneca, Aptevo Therapeutics, Glaxo Smith Kline, Pfizer, MedImmune, Astellas, SYNthorx, Bionomics, Sanofi Aventis, Novartis, Ipsen); D.P. (Honoraria: Astellas, Ipsen, Novartis; Advisory/Consulting: Pfizer, Merck Sharp & Dhome, Bristol-Myers Squibb; Research Funding to institution: Medivation, Bristol-Myers Squibb, Merck Sharp & Dhome, Exelixis, Pfizer, Astellas, Bayer, SymVivo, Amgen; Travel: Bristol-Myers Squibb, Pfizer, Amgen); C.J.P. (Honoraria: Advanced Accelerator Applications, Astellas, AstraZeneza, Janssen, Pfizer; Travel support: Bayer, Jans-sen); S.S. (Grant funding to institution: AstraZeneca, Novartis, Amgen, Genentech, Merck Sharp and Dohme, Merck Serono; Honoraria: Merck Sharp and Dohme, Astra Zeneca and Bristol Myer Squibb); E.M.K. (Consulting or Advisory Role: Astellas Pharma, Janssen, Ipsen; Travel, Accommodations, Expenses: Astellas Pharma, Pfizer, Ipsen, Roche; Honoraria: Janssen, Ipsen, Astellas Pharma, Research Review; Research Funding: Astellas Pharma (institutional), AstraZeneca (institutional)); J Grummet (Honoraria: BK Ultrasound, Biobot, Mundipharma; Travel: Astellas; Owner of MRI PRO Pty Ltd., an online training platform)); L.F. (Grant funding to institution: Pimera). All other authors declare no competing interests. Funding Information: We wish to acknowledge the Traditional Owners of the lands on which these studies were done. We pay our respects to their Elders, past and present. We also acknowledge the members of the Prostate Cancer Research program, the patients, families, and consumers who support our research. We acknowledge the patient representatives, clinical co-ordi-nators, scientists, and clinicians, who contribute to the Melbourne Urological Research Alliance (MURAL) and its collection of patient-derived models. We acknowledge kConFab including kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics, and the Clinical Follow-Up Study (which has received funding from the NHMRC, the National Breast Cancer Foundation, Cancer Australia, and the National Institute of Health (USA)) for their contributions to this resource, and the many families who contribute to kConFab. We thank Mark McCabe, Chia-Ling Chan, and Alex Swarbrick for providing access to targeted DNA sequencing technology; Kathryn Alsop, Damien Bolton, Nathan Lawrentschuk, Ross Snow, and Sri Apu for provision of clinical samples; and Melissa Bullock for technical support. This work was supported by the National Health and Medical Research Council, Australia (1102752, 1090204, 1138242, 1185616, 1077799, 1156570, 1140222, 1059855, and 1121057; the US Department of Defense through the Prostate Cancer Research Program (G.P.R. W81XWH1810349; opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the Department of Defense); Department of Health and Human Services acting through the Victorian Cancer Agency (MCRF15023, MCRF18017, MCRF18012, MCRF17005, L.F. MCRF16007, CAPTIV Program); Prostate Cancer Foundation of Australia (YI 0417, PIRA1519, NCG1616); Peter MacCallum Cancer Foundation (1752); Monash University (Bridging Fellowship L.P.); the CASS Foundation (7139, 8669, 8575); the EJ Whitten Foundation; Movember Foundation (Global Action Plan 1); Movember and National Breast Cancer Foundation Collaboration Initiative Grant (MNBCF-17-012); Movember and MRFF UpFront PSMA Prostate Cancer Research Alliance (PCRA); the Peter and Lyndy White Foundation; and TissuPath Pathology. This research was supported by the Monash University Histology Platform, Monash University Animal Research Laboratories, Monash Biomedicine Discovery Institute Organoid Program, and the NeCTAR Research Cloud, a collaborative Australian research platform supported by the National Collaborative Research Infrastructure Strategy. Publisher Copyright: {\textcopyright} 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
month = aug,
day = "19",
doi = "10.1038/s41467-021-25175-5",
language = "English",
volume = "12",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}
