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Comprehensive characterization of 536 patient-derived xenograft models prioritizes candidates for targeted treatment

Author

Listed:
  • Hua Sun

    (Washington University in St. Louis
    Washington University in St. Louis)

  • Song Cao

    (Washington University in St. Louis
    Washington University in St. Louis)

  • R. Jay Mashl

    (Washington University in St. Louis
    Washington University in St. Louis)

  • Chia-Kuei Mo

    (Washington University in St. Louis
    Washington University in St. Louis)

  • Simone Zaccaria

    (Princeton University
    University College London Cancer Institute)

  • Michael C. Wendl

    (Washington University in St. Louis
    Washington University in St. Louis
    Washington University in St. Louis)

  • Sherri R. Davies

    (Washington University in St. Louis)

  • Matthew H. Bailey

    (Huntsman Cancer Institute, University of Utah)

  • Tina M. Primeau

    (Washington University in St. Louis)

  • Jeremy Hoog

    (Washington University in St. Louis)

  • Jacqueline L. Mudd

    (Washington University in St. Louis)

  • Dennis A. Dean

    (Inc., Cambridge)

  • Rajesh Patidar

    (Frederick National Laboratory for Cancer Research)

  • Li Chen

    (Frederick National Laboratory for Cancer Research)

  • Matthew A. Wyczalkowski

    (Washington University in St. Louis
    Washington University in St. Louis)

  • Reyka G. Jayasinghe

    (Washington University in St. Louis
    Washington University in St. Louis)

  • Fernanda Martins Rodrigues

    (Washington University in St. Louis
    Washington University in St. Louis)

  • Nadezhda V. Terekhanova

    (Washington University in St. Louis
    Washington University in St. Louis)

  • Yize Li

    (Washington University in St. Louis
    Washington University in St. Louis)

  • Kian-Huat Lim

    (Washington University in St. Louis
    Washington University in St. Louis)

  • Andrea Wang-Gillam

    (Washington University in St. Louis
    Washington University in St. Louis)

  • Brian A. Tine

    (Washington University in St. Louis
    Washington University in St. Louis)

  • Cynthia X. Ma

    (Washington University in St. Louis
    Washington University in St. Louis)

  • Rebecca Aft

    (Washington University in St. Louis)

  • Katherine C. Fuh

    (Washington University in St. Louis
    Washington University in St. Louis)

  • Julie K. Schwarz

    (Washington University in St. Louis
    Washington University in St. Louis)

  • Jose P. Zevallos

    (Washington University in St. Louis
    Washington University St. Louis)

  • Sidharth V. Puram

    (Washington University in St. Louis
    Washington University St. Louis)

  • John F. Dipersio

    (Washington University in St. Louis
    Washington University in St. Louis)

  • Brandi Davis-Dusenbery

    (Inc., Cambridge)

  • Matthew J. Ellis

    (Baylor College of Medicine)

  • Michael T. Lewis

    (Baylor College of Medicine)

  • Michael A. Davies

    (The University of Texas MD Anderson Cancer Center)

  • Meenhard Herlyn

    (The Wistar Institute)

  • Bingliang Fang

    (The University of Texas MD Anderson Cancer Center)

  • Jack A. Roth

    (The University of Texas MD Anderson Cancer Center)

  • Alana L. Welm

    (Huntsman Cancer Institute, University of Utah)

  • Bryan E. Welm

    (Huntsman Cancer Institute, University of Utah)

  • Funda Meric-Bernstam

    (The University of Texas MD Anderson Cancer Center)

  • Feng Chen

    (Washington University in St. Louis)

  • Ryan C. Fields

    (Washington University in St. Louis)

  • Shunqiang Li

    (Washington University in St. Louis
    Washington University in St. Louis)

  • Ramaswamy Govindan

    (Washington University in St. Louis
    Washington University in St. Louis)

  • James H. Doroshow

    (National Cancer Institute)

  • Jeffrey A. Moscow

    (National Cancer Institute)

  • Yvonne A. Evrard

    (Frederick National Laboratory for Cancer Research)

  • Jeffrey H. Chuang

    (The Jackson Laboratory for Genomic Medicine)

  • Benjamin J. Raphael

    (Princeton University)

  • Li Ding

    (Washington University in St. Louis
    Washington University in St. Louis
    Washington University in St. Louis
    Washington University in St. Louis)

Abstract

Development of candidate cancer treatments is a resource-intensive process, with the research community continuing to investigate options beyond static genomic characterization. Toward this goal, we have established the genomic landscapes of 536 patient-derived xenograft (PDX) models across 25 cancer types, together with mutation, copy number, fusion, transcriptomic profiles, and NCI-MATCH arms. Compared with human tumors, PDXs typically have higher purity and fit to investigate dynamic driver events and molecular properties via multiple time points from same case PDXs. Here, we report on dynamic genomic landscapes and pharmacogenomic associations, including associations between activating oncogenic events and drugs, correlations between whole-genome duplications and subclone events, and the potential PDX models for NCI-MATCH trials. Lastly, we provide a web portal having comprehensive pan-cancer PDX genomic profiles and source code to facilitate identification of more druggable events and further insights into PDXs’ recapitulation of human tumors.

Suggested Citation

  • Hua Sun & Song Cao & R. Jay Mashl & Chia-Kuei Mo & Simone Zaccaria & Michael C. Wendl & Sherri R. Davies & Matthew H. Bailey & Tina M. Primeau & Jeremy Hoog & Jacqueline L. Mudd & Dennis A. Dean & Raj, 2021. "Comprehensive characterization of 536 patient-derived xenograft models prioritizes candidates for targeted treatment," Nature Communications, Nature, vol. 12(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25177-3
    DOI: 10.1038/s41467-021-25177-3
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    Cited by:

    1. Simonetta M. Leto & Elena Grassi & Marco Avolio & Valentina Vurchio & Francesca Cottino & Martina Ferri & Eugenia R. Zanella & Sofia Borgato & Giorgio Corti & Laura Blasio & Desiana Somale & Marianela, 2024. "XENTURION is a population-level multidimensional resource of xenografts and tumoroids from metastatic colorectal cancer patients," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    2. Funan He & Abhik M. Bandyopadhyay & Laura J. Klesse & Anna Rogojina & Sang H. Chun & Erin Butler & Taylor Hartshorne & Trevor Holland & Dawn Garcia & Korri Weldon & Luz-Nereida Perez Prado & Anne-Mari, 2023. "Genomic profiling of subcutaneous patient-derived xenografts reveals immune constraints on tumor evolution in childhood solid cancer," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    3. Ashenafi Bulle & Peng Liu & Kuljeet Seehra & Sapana Bansod & Yali Chen & Kiran Zahra & Vikas Somani & Iftikhar Ali Khawar & Hung-Po Chen & Paarth B. Dodhiawala & Lin Li & Yutong Geng & Chia-Kuei Mo & , 2024. "Combined KRAS-MAPK pathway inhibitors and HER2-directed drug conjugate is efficacious in pancreatic cancer," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    4. Sebastijan Hobor & Maise Al Bakir & Crispin T. Hiley & Marcin Skrzypski & Alexander M. Frankell & Bjorn Bakker & Thomas B. K. Watkins & Aleksandra Markovets & Jonathan R. Dry & Andrew P. Brown & Jaspe, 2024. "Mixed responses to targeted therapy driven by chromosomal instability through p53 dysfunction and genome doubling," Nature Communications, Nature, vol. 15(1), pages 1-21, December.

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