IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v6y2015i1d10.1038_ncomms8956.html
   My bibliography  Save this article

RETRACTED ARTICLE: An apoptosis-enhancing drug overcomes platinum resistance in a tumour-initiating subpopulation of ovarian cancer

Author

Listed:
  • D. M. Janzen

    (David Geffen School of Medicine, University of California, Los Angeles)

  • E. Tiourin

    (David Geffen School of Medicine, University of California, Los Angeles)

  • J. A. Salehi

    (David Geffen School of Medicine, University of California, Los Angeles)

  • D. Y. Paik

    (David Geffen School of Medicine, University of California, Los Angeles)

  • J. Lu

    (Cell and Developmental Biology, University of California, Los Angeles)

  • M. Pellegrini

    (Cell and Developmental Biology, University of California, Los Angeles
    Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles)

  • S. Memarzadeh

    (David Geffen School of Medicine, University of California, Los Angeles
    Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles
    The VA Greater Los Angeles Health Care System)

Abstract

High-grade serous ovarian cancers (HGSCs) are deadly malignancies that relapse despite carboplatin chemotherapy. Here we show that 16 independent primary HGSC samples contain a CA125-negative population enriched for carboplatin-resistant cancer initiating cells. Transcriptome analysis reveals upregulation of homologous recombination DNA repair and anti-apoptotic signals in this population. While treatment with carboplatin enriches for CA125-negative cells, co-treatment with carboplatin and birinapant eliminates these cells in HGSCs expressing high levels of the inhibitor of apoptosis protein cIAP in the CA125-negative population. Birinapant sensitizes CA125-negative cells to carboplatin by mediating degradation of cIAP causing cleavage of caspase 8 and restoration of apoptosis. This co-therapy significantly improves disease-free survival in vivo compared with either therapy alone in tumour-bearing mice. These findings suggest that therapeutic strategies that target CA125-negative cells may be useful in the treatment of HGSC.

Suggested Citation

  • D. M. Janzen & E. Tiourin & J. A. Salehi & D. Y. Paik & J. Lu & M. Pellegrini & S. Memarzadeh, 2015. "RETRACTED ARTICLE: An apoptosis-enhancing drug overcomes platinum resistance in a tumour-initiating subpopulation of ovarian cancer," Nature Communications, Nature, vol. 6(1), pages 1-18, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8956
    DOI: 10.1038/ncomms8956
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms8956
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms8956?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8956. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.