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ERG induces taxane resistance in castration-resistant prostate cancer

Author

Listed:
  • Giuseppe Galletti

    (Weill Cornell Medical College)

  • Alexandre Matov

    (Weill Cornell Medical College
    University for Information Science and Technology St Paul the Apostle)

  • Himisha Beltran

    (Weill Cornell Medical College
    Institute of Precision Medicine of Weill Cornell Medical College and New York-Presbyterian Hospital)

  • Jacqueline Fontugne

    (Weill Cornell Medical College)

  • Juan Miguel Mosquera

    (Institute of Precision Medicine of Weill Cornell Medical College and New York-Presbyterian Hospital
    Weill Cornell Medical College)

  • Cynthia Cheung

    (Weill Cornell Medical College)

  • Theresa Y. MacDonald

    (Weill Cornell Medical College)

  • Matthew Sung

    (Weill Cornell Medical College)

  • Sandra O’Toole

    (Royal Prince Alfred Hospital, Camperdown
    The Kinghorn Cancer Centre / Garvan Institute of Medical Research, Victoria St, Darlinghurst)

  • James G. Kench

    (Royal Prince Alfred Hospital, Camperdown
    The Kinghorn Cancer Centre / Garvan Institute of Medical Research, Victoria St, Darlinghurst)

  • Sung Suk Chae

    (Weill Cornell Medical College)

  • Dragi Kimovski

    (University for Information Science and Technology St Paul the Apostle)

  • Scott T. Tagawa

    (Weill Cornell Medical College
    Weill Cornell Cancer Center)

  • David M. Nanus

    (Weill Cornell Medical College
    Weill Cornell Cancer Center)

  • Mark A. Rubin

    (Institute of Precision Medicine of Weill Cornell Medical College and New York-Presbyterian Hospital
    Weill Cornell Medical College
    Weill Cornell Cancer Center)

  • Lisa G. Horvath

    (Royal Prince Alfred Hospital, Camperdown
    The Kinghorn Cancer Centre / Garvan Institute of Medical Research, Victoria St, Darlinghurst
    Chris O’Brien Lifehouse, Royal Prince Alfred Hospital and the University of Sydney, Camperdown)

  • Paraskevi Giannakakou

    (Weill Cornell Medical College
    Weill Cornell Cancer Center)

  • David S. Rickman

    (Institute of Precision Medicine of Weill Cornell Medical College and New York-Presbyterian Hospital
    Weill Cornell Medical College
    Weill Cornell Cancer Center)

Abstract

Taxanes are the only chemotherapies used to treat patients with metastatic castration-resistant prostate cancer (CRPC). Despite the initial efficacy of taxanes in treating CRPC, all patients ultimately fail due to the development of drug resistance. In this study, we show that ERG overexpression in in vitro and in vivo models of CRPC is associated with decreased sensitivity to taxanes. ERG affects several parameters of microtubule dynamics and inhibits effective drug-target engagement of docetaxel or cabazitaxel with tubulin. Finally, analysis of a cohort of 34 men with metastatic CRPC treated with docetaxel chemotherapy reveals that ERG-overexpressing prostate cancers have twice the chance of docetaxel resistance than ERG-negative cancers. Our data suggest that ERG plays a role beyond regulating gene expression and functions outside the nucleus to cooperate with tubulin towards taxane insensitivity. Determining ERG rearrangement status may aid in patient selection for docetaxel or cabazitaxel therapy and/or influence co-targeting approaches.

Suggested Citation

  • Giuseppe Galletti & Alexandre Matov & Himisha Beltran & Jacqueline Fontugne & Juan Miguel Mosquera & Cynthia Cheung & Theresa Y. MacDonald & Matthew Sung & Sandra O’Toole & James G. Kench & Sung Suk C, 2014. "ERG induces taxane resistance in castration-resistant prostate cancer," Nature Communications, Nature, vol. 5(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6548
    DOI: 10.1038/ncomms6548
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