IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v7y2016i1d10.1038_ncomms10690.html
   My bibliography  Save this article

Diverse drug-resistance mechanisms can emerge from drug-tolerant cancer persister cells

Author

Listed:
  • Michael Ramirez

    (University of California, San Francisco
    Green Center for Systems Biology, University of Texas Southwestern Medical Center)

  • Satwik Rajaram

    (University of California, San Francisco
    Green Center for Systems Biology, University of Texas Southwestern Medical Center)

  • Robert J. Steininger

    (Green Center for Systems Biology, University of Texas Southwestern Medical Center)

  • Daria Osipchuk

    (University of California, San Francisco)

  • Maike A. Roth

    (University of California, San Francisco)

  • Leanna S. Morinishi

    (University of California, San Francisco)

  • Louise Evans

    (University of California, San Francisco)

  • Weiyue Ji

    (University of California, San Francisco)

  • Chien-Hsiang Hsu

    (University of California, San Francisco)

  • Kevin Thurley

    (University of California, San Francisco)

  • Shuguang Wei

    (University of Texas Southwestern Medical Center)

  • Anwu Zhou

    (University of Texas Southwestern Medical Center)

  • Prasad R. Koduru

    (University of Texas Southwestern Medical Center)

  • Bruce A. Posner

    (University of Texas Southwestern Medical Center)

  • Lani F. Wu

    (University of California, San Francisco
    Green Center for Systems Biology, University of Texas Southwestern Medical Center)

  • Steven J. Altschuler

    (University of California, San Francisco
    Green Center for Systems Biology, University of Texas Southwestern Medical Center)

Abstract

Cancer therapy has traditionally focused on eliminating fast-growing populations of cells. Yet, an increasing body of evidence suggests that small subpopulations of cancer cells can evade strong selective drug pressure by entering a ‘persister’ state of negligible growth. This drug-tolerant state has been hypothesized to be part of an initial strategy towards eventual acquisition of bona fide drug-resistance mechanisms. However, the diversity of drug-resistance mechanisms that can expand from a persister bottleneck is unknown. Here we compare persister-derived, erlotinib-resistant colonies that arose from a single, EGFR-addicted lung cancer cell. We find, using a combination of large-scale drug screening and whole-exome sequencing, that our erlotinib-resistant colonies acquired diverse resistance mechanisms, including the most commonly observed clinical resistance mechanisms. Thus, the drug-tolerant persister state does not limit—and may even provide a latent reservoir of cells for—the emergence of heterogeneous drug-resistance mechanisms.

Suggested Citation

  • Michael Ramirez & Satwik Rajaram & Robert J. Steininger & Daria Osipchuk & Maike A. Roth & Leanna S. Morinishi & Louise Evans & Weiyue Ji & Chien-Hsiang Hsu & Kevin Thurley & Shuguang Wei & Anwu Zhou , 2016. "Diverse drug-resistance mechanisms can emerge from drug-tolerant cancer persister cells," Nature Communications, Nature, vol. 7(1), pages 1-8, April.
  • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10690
    DOI: 10.1038/ncomms10690
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms10690
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/ncomms10690?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. Jun Dai & Shuyu Zheng & Matías M. Falco & Jie Bao & Johanna Eriksson & Sanna Pikkusaari & Sofia Forstén & Jing Jiang & Wenyu Wang & Luping Gao & Fernando Perez-Villatoro & Olli Dufva & Khalid Saeed & , 2024. "Tracing back primed resistance in cancer via sister cells," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Franziska Haderk & Yu-Ting Chou & Lauren Cech & Celia Fernández-Méndez & Johnny Yu & Victor Olivas & Ismail M. Meraz & Dora Barbosa Rabago & D. Lucas Kerr & Carlos Gomez & David V. Allegakoen & Juan G, 2024. "Focal adhesion kinase-YAP signaling axis drives drug-tolerant persister cells and residual disease in lung cancer," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    3. Sarah Figarol & Célia Delahaye & Rémi Gence & Aurélia Doussine & Juan Pablo Cerapio & Mathylda Brachais & Claudine Tardy & Nicolas Béry & Raghda Asslan & Jacques Colinge & Jean-Philippe Villemin & Ant, 2024. "Farnesyltransferase inhibition overcomes oncogene-addicted non-small cell lung cancer adaptive resistance to targeted therapies," Nature Communications, Nature, vol. 15(1), pages 1-15, 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.

    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:7:y:2016:i:1:d:10.1038_ncomms10690. 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.