IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v6y2015i1d10.1038_ncomms7139.html
   My bibliography  Save this article

Temporally sequenced anticancer drugs overcome adaptive resistance by targeting a vulnerable chemotherapy-induced phenotypic transition

Author

Listed:
  • Aaron Goldman

    (Harvard Medical School
    Harvard-MIT Division of Health Sciences and Technology
    Brigham and Women’s Hospital)

  • Biswanath Majumder

    (India Innovation Research Center
    Mitra Biotech Pvt Ltd, Narayana Nethrayala)

  • Andrew Dhawan

    (School of Medicine, Queen’s University)

  • Sudharshan Ravi

    (Brigham and Women’s Hospital)

  • David Goldman

    (7730E BlackCrest Pl.)

  • Mohammad Kohandel

    (University of Waterloo)

  • Pradip K. Majumder

    (India Innovation Research Center
    Mitra Biotech Pvt Ltd, Narayana Nethrayala)

  • Shiladitya Sengupta

    (Harvard Medical School
    Harvard-MIT Division of Health Sciences and Technology
    Brigham and Women’s Hospital
    Dana Farber Cancer Institute)

Abstract

Understanding the emerging models of adaptive resistance is key to overcoming cancer chemotherapy failure. Using human breast cancer explants, in vitro cell lines, mouse in vivo studies and mathematical modelling, here we show that exposure to a taxane induces phenotypic cell state transition towards a favoured transient CD44HiCD24Hi chemotherapy-tolerant state. This state is associated with a clustering of CD44 and CD24 in membrane lipid rafts, leading to the activation of Src Family Kinase (SFK)/hemopoietic cell kinase (Hck) and suppression of apoptosis. The use of pharmacological inhibitors of SFK/Hck in combination with taxanes in a temporally constrained manner, where the kinase inhibitor is administered post taxane treatment, but not when co-administered, markedly sensitizes the chemotolerant cells to the chemotherapy. This approach of harnessing chemotherapy-induced phenotypic cell state transition for improving antitumour outcome could emerge as a translational strategy for the management of cancer.

Suggested Citation

  • Aaron Goldman & Biswanath Majumder & Andrew Dhawan & Sudharshan Ravi & David Goldman & Mohammad Kohandel & Pradip K. Majumder & Shiladitya Sengupta, 2015. "Temporally sequenced anticancer drugs overcome adaptive resistance by targeting a vulnerable chemotherapy-induced phenotypic transition," Nature Communications, Nature, vol. 6(1), pages 1-13, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7139
    DOI: 10.1038/ncomms7139
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms7139
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms7139?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
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Nikolay Bessonov & Guillaume Pinna & Andrey Minarsky & Annick Harel-Bellan & Nadya Morozova, 2019. "Mathematical modeling reveals the factors involved in the phenomena of cancer stem cells stabilization," PLOS ONE, Public Library of Science, vol. 14(11), pages 1-24, November.

    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_ncomms7139. 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.