IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v11y2020i1d10.1038_s41467-020-17697-1.html
   My bibliography  Save this article

PLK1 inhibition exhibits strong anti-tumoral activity in CCND1-driven breast cancer metastases with acquired palbociclib resistance

Author

Listed:
  • Elodie Montaudon

    (Translational Research Department, Institut Curie)

  • Joanna Nikitorowicz-Buniak

    (Institute of Cancer Research)

  • Laura Sourd

    (Translational Research Department, Institut Curie)

  • Ludivine Morisset

    (Translational Research Department, Institut Curie)

  • Rania El Botty

    (Translational Research Department, Institut Curie)

  • Léa Huguet

    (Translational Research Department, Institut Curie)

  • Ahmed Dahmani

    (Translational Research Department, Institut Curie)

  • Pierre Painsec

    (Translational Research Department, Institut Curie)

  • Fariba Nemati

    (Translational Research Department, Institut Curie)

  • Sophie Vacher

    (Department of Genetics, Institut Curie)

  • Walid Chemlali

    (Department of Genetics, Institut Curie)

  • Julien Masliah-Planchon

    (Department of Genetics, Institut Curie)

  • Sophie Château-Joubert

    (Alfort Veterinary School)

  • Camilla Rega

    (Institute of Cancer Research)

  • Mariana Ferreira Leal

    (Institute of Cancer Research)

  • Nikiana Simigdala

    (Institute of Cancer Research)

  • Sunil Pancholi

    (Institute of Cancer Research)

  • Ricardo Ribas

    (Institute of Cancer Research)

  • André Nicolas

    (Department of Pathology, Institut Curie)

  • Didier Meseure

    (Department of Pathology, Institut Curie)

  • Anne Vincent-Salomon

    (Department of Pathology, Institut Curie)

  • Cécile Reyes

    (Translational Research Department, Institut Curie)

  • Audrey Rapinat

    (Translational Research Department, Institut Curie)

  • David Gentien

    (Translational Research Department, Institut Curie)

  • Thibaut Larcher

    (INRA, APEX-PAnTher, Oniris)

  • Mylène Bohec

    (Genomics of Excellence (ICGex) Platform, Institut Curie Research Center)

  • Sylvain Baulande

    (Genomics of Excellence (ICGex) Platform, Institut Curie Research Center)

  • Virginie Bernard

    (Department of Genetics, Institut Curie)

  • Didier Decaudin

    (Translational Research Department, Institut Curie
    Department of Medical Oncology, Institut Curie)

  • Florence Coussy

    (Translational Research Department, Institut Curie
    Department of Medical Oncology, Institut Curie)

  • Muriel Le Romancer

    (Inserm U1052, Centre de Recherche en Cancérologie de Lyon)

  • Guillaume Dutertre

    (Department of Surgery, Institut Curie)

  • Zakia Tariq

    (Department of Genetics, Institut Curie)

  • Paul Cottu

    (Department of Medical Oncology, Institut Curie)

  • Keltouma Driouch

    (Department of Genetics, Institut Curie)

  • Ivan Bièche

    (Department of Genetics, Institut Curie)

  • Lesley-Ann Martin

    (Institute of Cancer Research)

  • Elisabetta Marangoni

    (Translational Research Department, Institut Curie)

Abstract

A significant proportion of patients with oestrogen receptor (ER) positive breast cancers (BC) develop resistance to endocrine treatments (ET) and relapse with metastatic disease. Here we perform whole exome sequencing and gene expression analysis of matched primary breast tumours and bone metastasis-derived patient-derived xenografts (PDX). Transcriptomic analyses reveal enrichment of the G2/M checkpoint and up-regulation of Polo-like kinase 1 (PLK1) in PDX. PLK1 inhibition results in tumour shrinkage in highly proliferating CCND1-driven PDX, including different RB-positive PDX with acquired palbociclib resistance. Mechanistic studies in endocrine resistant cell lines, suggest an ER-independent function of PLK1 in regulating cell proliferation. Finally, in two independent clinical cohorts of ER positive BC, we find a strong association between high expression of PLK1 and a shorter metastases-free survival and poor response to anastrozole. In conclusion, our findings support clinical development of PLK1 inhibitors in patients with advanced CCND1-driven BC, including patients progressing on palbociclib treatment.

Suggested Citation

  • Elodie Montaudon & Joanna Nikitorowicz-Buniak & Laura Sourd & Ludivine Morisset & Rania El Botty & Léa Huguet & Ahmed Dahmani & Pierre Painsec & Fariba Nemati & Sophie Vacher & Walid Chemlali & Julien, 2020. "PLK1 inhibition exhibits strong anti-tumoral activity in CCND1-driven breast cancer metastases with acquired palbociclib resistance," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17697-1
    DOI: 10.1038/s41467-020-17697-1
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-020-17697-1
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-020-17697-1?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. Petra Brugge & Sarah C. Moser & Ivan Bièche & Petra Kristel & Sabrina Ibadioune & Alexandre Eeckhoutte & Roebi Bruijn & Eline Burg & Catrin Lutz & Stefano Annunziato & Julian Ruiter & Julien Masliah P, 2023. "Homologous recombination deficiency derived from whole-genome sequencing predicts platinum response in triple-negative breast cancers," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Rania El-Botty & Ludivine Morriset & Elodie Montaudon & Zakia Tariq & Anne Schnitzler & Marina Bacci & Nicla Lorito & Laura Sourd & Léa Huguet & Ahmed Dahmani & Pierre Painsec & Heloise Derrien & Soph, 2023. "Oxidative phosphorylation is a metabolic vulnerability of endocrine therapy and palbociclib resistant metastatic breast cancers," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    3. Ozge Saatci & Metin Cetin & Meral Uner & Unal Metin Tokat & Ioulia Chatzistamou & Pelin Gulizar Ersan & Elodie Montaudon & Aytekin Akyol & Sercan Aksoy & Aysegul Uner & Elisabetta Marangoni & Mathew S, 2023. "Toxic PARP trapping upon cAMP-induced DNA damage reinstates the efficacy of endocrine therapy and CDK4/6 inhibitors in treatment-refractory ER+ breast cancer," Nature Communications, Nature, vol. 14(1), pages 1-20, 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:11:y:2020:i:1:d:10.1038_s41467-020-17697-1. 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.