The MURAL collection of prostate cancer patient-derived xenografts enables discovery through preclinical models of uro-oncology

Risbridger, Gail P.; Clark, Ashlee K.; Porter, Laura H.; Toivanen, Roxanne; Bakshi, Andrew; Lister, Natalie L.; Pook, David; Pezaro, Carmel J.; Sandhu, Shahneen; Keerthikumar, Shivakumar; Urban, Rosalia Quezada; Papargiris, Melissa; Kraska, Jenna; Madsen, Heather B.; Wang, Hong; Richards, Michelle G.; Niranjan, Birunthi; O’Dea, Samantha; Teng, Linda; Wheelahan, William; Li, Zhuoer; Choo, Nicholas; Ouyang, John F.; Thorne, Heather; Devereux, Lisa; Hicks, Rodney J.; Sengupta, Shomik; Harewood, Laurence; Iddawala, Mahesh; Azad, Arun A.; Goad, Jeremy; Grummet, Jeremy; Kourambas, John; Kwan, Edmond M.; Moon, Daniel; Murphy, Declan G.; Pedersen, John; Clouston, David; Norden, Sam; Ryan, Andrew; Furic, Luc; Goode, David L.; Frydenberg, Mark; Lawrence, Mitchell G.; Taylor, Renea A.

The MURAL collection of prostate cancer patient-derived xenografts enables discovery through preclinical models of uro-oncology

Gail P. Risbridger (), Ashlee K. Clark, Laura H. Porter, Roxanne Toivanen, Andrew Bakshi, Natalie L. Lister, David Pook, Carmel J. Pezaro, Shahneen Sandhu, Shivakumar Keerthikumar, Rosalia Quezada Urban, Melissa Papargiris, Jenna Kraska, Heather B. Madsen, Hong Wang, Michelle G. Richards, Birunthi Niranjan, Samantha O’Dea, Linda Teng, William Wheelahan, Zhuoer Li, Nicholas Choo, John F. Ouyang, Heather Thorne, Lisa Devereux, Rodney J. Hicks, Shomik Sengupta, Laurence Harewood, Mahesh Iddawala, Arun A. Azad, Jeremy Goad, Jeremy Grummet, John Kourambas, Edmond M. Kwan, Daniel Moon, Declan G. Murphy, John Pedersen, David Clouston, Sam Norden, Andrew Ryan, Luc Furic, David L. Goode, Mark Frydenberg, Mitchell G. Lawrence and Renea A. Taylor ()
Additional contact information
Gail P. Risbridger: Monash University
Ashlee K. Clark: Monash University
Laura H. Porter: Monash University
Roxanne Toivanen: Monash University
Andrew Bakshi: Monash University
Natalie L. Lister: Monash University
David Pook: Monash University
Carmel J. Pezaro: Monash University
Shahneen Sandhu: The University of Melbourne
Shivakumar Keerthikumar: Cancer Research Division, Peter MacCallum Cancer Centre
Rosalia Quezada Urban: Cancer Research Division, Peter MacCallum Cancer Centre
Melissa Papargiris: Monash University
Jenna Kraska: Monash University
Heather B. Madsen: Monash University
Hong Wang: Monash University
Michelle G. Richards: Monash University
Birunthi Niranjan: Monash University
Samantha O’Dea: Monash University
Linda Teng: Monash University
William Wheelahan: Monash University
Zhuoer Li: Monash University
Nicholas Choo: Monash University
John F. Ouyang: Duke-National University of Singapore Medical School
Heather Thorne: Cancer Research Division, Peter MacCallum Cancer Centre
Lisa Devereux: Cancer Research Division, Peter MacCallum Cancer Centre
Rodney J. Hicks: Peter MacCallum Cancer Center
Shomik Sengupta: Eastern Health and Monash University Eastern Health Clinical School
Laurence Harewood: Epworth Healthcare
Mahesh Iddawala: Monash University
Arun A. Azad: The University of Melbourne
Jeremy Goad: The University of Melbourne
Jeremy Grummet: Epworth Healthcare
John Kourambas: Casey Hospital
Edmond M. Kwan: Monash University
Daniel Moon: Epworth Healthcare
Declan G. Murphy: The University of Melbourne
John Pedersen: Monash University
David Clouston: TissuPath
Sam Norden: TissuPath
Andrew Ryan: TissuPath
Luc Furic: Monash University
David L. Goode: Cancer Research Division, Peter MacCallum Cancer Centre
Mark Frydenberg: Monash University
Mitchell G. Lawrence: Monash University
Renea A. Taylor: Cancer Research Division, Peter MacCallum Cancer Centre

Nature Communications, 2021, vol. 12, issue 1, 1-17

Abstract: 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-naïve 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.

Date: 2021
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DOI: 10.1038/s41467-021-25175-5

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