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 WheelahanZhuoer 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, Renea A. Taylor

Research output: Contribution to journalArticleResearchpeer-review

4 Citations (Scopus)

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.

Original languageEnglish
Article number5049
JournalNature Communications
Volume12
Issue number1
DOIs
Publication statusPublished - 19 Aug 2021

Cite this