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-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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Aug 19, 2021
- Source ID
- 10.1038/s41467-021-25175-5
Entities
People
- Andrew Bakshi
- Andrew Ryan
- Arun Azad
- Ashlee K. Clark
- Birunthi Niranjan
- Carmel J. Pezaro
- Daniel Moon
- David Clouston
- David L. Goode
- David Pook
- Declan G Murphy
- Edmond M Kwan
- Gail Petuna Risbridger
- Heather B. Madsen
- Heather Thorne
- Hong Wang
- Jenna Kraska
- Jeremy Goad
- Jeremy Grummet
- John F Ouyang
- John Kourambas
- John Pedersen
- Laura H. Porter
- Laurence Harewood
- Linda Teng
- Lisa Devereux
- Luc Furic
- Mahesh Iddawala
- Mark Frydenberg
- Melissa Papargiris
- Michelle G. Richards
- Mitchell G Lawrence
- Natalie L. Lister
- Nicholas Choo
- Renea A Taylor
- Rodney J. Hicks
- Rosalia Quezada Urban
- Roxanne Toivanen
- Sam Norden
- Samantha O’dea
- Shahneen K Sandhu
- Shivakumar Keerthikumar
- Shomik Sengupta
- William Wheelahan
- Zhuoer Li
Organizations
- National Health and Medical Research Council
- United States Department of Defense