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

Author

Listed:
  • Gail P. Risbridger

    (Monash University
    Cancer Research Division, Peter MacCallum Cancer Centre)

  • Ashlee K. Clark

    (Monash University)

  • Laura H. Porter

    (Monash University)

  • Roxanne Toivanen

    (Monash University
    Cancer Research Division, Peter MacCallum Cancer Centre
    The University of Melbourne)

  • Andrew Bakshi

    (Monash University
    Cancer Research Division, Peter MacCallum Cancer Centre
    The University of Melbourne
    Peter MacCallum Cancer Centre)

  • Natalie L. Lister

    (Monash University)

  • David Pook

    (Monash University
    Monash University
    Monash Health)

  • Carmel J. Pezaro

    (Monash University
    Eastern Health and Monash University Eastern Health Clinical School
    Sheffield Teaching Hospitals NHS Foundation Trust)

  • Shahneen Sandhu

    (The University of Melbourne
    Peter MacCallum Cancer Centre
    Cancer Tissue Collection After Death (CASCADE) Program)

  • Shivakumar Keerthikumar

    (Cancer Research Division, Peter MacCallum Cancer Centre
    The University of Melbourne
    Peter MacCallum Cancer Centre)

  • Rosalia Quezada Urban

    (Cancer Research Division, Peter MacCallum Cancer Centre
    The University of Melbourne
    Peter MacCallum Cancer Centre)

  • Melissa Papargiris

    (Monash University
    Monash University)

  • Jenna Kraska

    (Monash University
    Cancer Research Division, Peter MacCallum Cancer Centre
    Monash University)

  • Heather B. Madsen

    (Monash University
    Cancer Research Division, Peter MacCallum Cancer Centre
    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
    The University of Melbourne)

  • Lisa Devereux

    (Cancer Research Division, Peter MacCallum Cancer Centre
    The University of Melbourne)

  • Rodney J. Hicks

    (Peter MacCallum Cancer Center)

  • Shomik Sengupta

    (Eastern Health and Monash University Eastern Health Clinical School
    The University of Melbourne
    The University of Melbourne
    Epworth Healthcare)

  • Laurence Harewood

    (Epworth Healthcare
    The University of Melbourne)

  • Mahesh Iddawala

    (Monash University
    Monash University)

  • Arun A. Azad

    (The University of Melbourne
    Peter MacCallum Cancer Centre)

  • Jeremy Goad

    (The University of Melbourne
    Epworth Healthcare
    The University of Melbourne)

  • Jeremy Grummet

    (Epworth Healthcare
    Monash University
    Australian Urology Associates)

  • John Kourambas

    (Casey Hospital)

  • Edmond M. Kwan

    (Monash University
    Monash Health)

  • Daniel Moon

    (Epworth Healthcare
    The University of Melbourne
    Australian Urology Associates
    Monash University)

  • Declan G. Murphy

    (The University of Melbourne
    Epworth Healthcare
    The University of Melbourne)

  • John Pedersen

    (Monash University
    TissuPath)

  • David Clouston

    (TissuPath)

  • Sam Norden

    (TissuPath)

  • Andrew Ryan

    (TissuPath)

  • Luc Furic

    (Monash University
    Cancer Research Division, Peter MacCallum Cancer Centre
    The University of Melbourne)

  • David L. Goode

    (Cancer Research Division, Peter MacCallum Cancer Centre
    The University of Melbourne
    Peter MacCallum Cancer Centre)

  • Mark Frydenberg

    (Monash University
    Epworth Healthcare
    Australian Urology Associates
    Monash University)

  • Mitchell G. Lawrence

    (Monash University
    Cancer Research Division, Peter MacCallum Cancer Centre
    The University of Melbourne)

  • Renea A. Taylor

    (Cancer Research Division, Peter MacCallum Cancer Centre
    The University of Melbourne
    Monash University)

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.

Suggested Citation

  • 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 Quez, 2021. "The MURAL collection of prostate cancer patient-derived xenografts enables discovery through preclinical models of uro-oncology," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25175-5
    DOI: 10.1038/s41467-021-25175-5
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    Cited by:

    1. L. H. Porter & J. J. Zhu & N. L. Lister & S. G. Harrison & S. Keerthikumar & D. L. Goode & R. Quezada Urban & D. J. Byrne & A. Azad & I. Vela & M. S. Hofman & P. J. Neeson & P. K. Darcy & J. A. Trapan, 2023. "Low-dose carboplatin modifies the tumor microenvironment to augment CAR T cell efficacy in human prostate cancer models," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Zifeng Wang & Scott L. Townley & Songqi Zhang & Mingyu Liu & Muqing Li & Maryam Labaf & Susan Patalano & Kavita Venkataramani & Kellee R. Siegfried & Jill A. Macoska & Dong Han & Shuai Gao & Gail P. R, 2024. "FOXA2 rewires AP-1 for transcriptional reprogramming and lineage plasticity in prostate cancer," Nature Communications, Nature, vol. 15(1), pages 1-20, December.

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