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

2021

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

Quezada Urban, Rosalia

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

Journal Article

Research Support, Non-U.S. Gov't

Research Support, U.S. Gov't, Non-P.H.S.

0000-0003-3089-4028

0000-0002-1239-1577

0000-0003-2435-5888

0000-0002-0758-0824

0000-0001-7350-5622

0000-0002-7053-680X

0000-0002-7500-5899

0000-0002-1893-9812

0000-0001-9520-3000

0000-0003-2609-2380

10.1038/s41467-021-25175-5

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.

link

Nature Communications 2021; 12(1): 5049

Nature Communications