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Reversible and adaptive resistance to BRAF(V600E) inhibition in melanoma

Author

Listed:
  • Chong Sun

    (Cancer Systems Biology Centre and Cancer Genomics Centre Netherlands, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands)

  • Liqin Wang

    (Cancer Systems Biology Centre and Cancer Genomics Centre Netherlands, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands)

  • Sidong Huang

    (Cancer Systems Biology Centre and Cancer Genomics Centre Netherlands, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    The Rosalind and Morris Goodman Cancer Centre, McGill University, Montreal, Quebec H3G 1Y6, Canada)

  • Guus J. J. E. Heynen

    (Cancer Systems Biology Centre and Cancer Genomics Centre Netherlands, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands)

  • Anirudh Prahallad

    (Cancer Systems Biology Centre and Cancer Genomics Centre Netherlands, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands)

  • Caroline Robert

    (Institut Gustave Roussy, 114 Rue Edouard Vaillant, 94800 Villejuif, France)

  • John Haanen

    (Cancer Systems Biology Centre and Cancer Genomics Centre Netherlands, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands)

  • Christian Blank

    (Cancer Systems Biology Centre and Cancer Genomics Centre Netherlands, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands)

  • Jelle Wesseling

    (Cancer Systems Biology Centre and Cancer Genomics Centre Netherlands, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands)

  • Stefan M. Willems

    (Cancer Systems Biology Centre and Cancer Genomics Centre Netherlands, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands)

  • Davide Zecchin

    (University of Torino, Str prov 142 Km 3.95, 10060 Candiolo, Torino, Italy
    Candiolo Cancer Institute – FPO, IRCCS, Str prov 142 Km 3.95, 10060 Candiolo, Torino, Italy)

  • Sebastijan Hobor

    (Candiolo Cancer Institute – FPO, IRCCS, Str prov 142 Km 3.95, 10060 Candiolo, Torino, Italy)

  • Prashanth K. Bajpe

    (Cancer Systems Biology Centre and Cancer Genomics Centre Netherlands, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands)

  • Cor Lieftink

    (Cancer Systems Biology Centre and Cancer Genomics Centre Netherlands, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands)

  • Christina Mateus

    (Institut Gustave Roussy, 114 Rue Edouard Vaillant, 94800 Villejuif, France)

  • Stephan Vagner

    (Institut Gustave Roussy, 114 Rue Edouard Vaillant, 94800 Villejuif, France)

  • Wipawadee Grernrum

    (Cancer Systems Biology Centre and Cancer Genomics Centre Netherlands, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands)

  • Ingrid Hofland

    (Cancer Systems Biology Centre and Cancer Genomics Centre Netherlands, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands)

  • Andreas Schlicker

    (Cancer Systems Biology Centre and Cancer Genomics Centre Netherlands, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands)

  • Lodewyk F. A. Wessels

    (Cancer Systems Biology Centre and Cancer Genomics Centre Netherlands, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands)

  • Roderick L. Beijersbergen

    (Cancer Systems Biology Centre and Cancer Genomics Centre Netherlands, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands)

  • Alberto Bardelli

    (University of Torino, Str prov 142 Km 3.95, 10060 Candiolo, Torino, Italy
    Candiolo Cancer Institute – FPO, IRCCS, Str prov 142 Km 3.95, 10060 Candiolo, Torino, Italy
    FIRC Institute of Molecular Oncology (IFOM), 20139 Milano, Italy)

  • Federica Di Nicolantonio

    (University of Torino, Str prov 142 Km 3.95, 10060 Candiolo, Torino, Italy
    Candiolo Cancer Institute – FPO, IRCCS, Str prov 142 Km 3.95, 10060 Candiolo, Torino, Italy)

  • Alexander M. M. Eggermont

    (Institut Gustave Roussy, 114 Rue Edouard Vaillant, 94800 Villejuif, France)

  • Rene Bernards

    (Cancer Systems Biology Centre and Cancer Genomics Centre Netherlands, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands)

Abstract

Patients with melanomas carrying an activating BRAF mutation respond to treatment with BRAF inhibitors although resistance to the inhibitor usually emerges; this resistance is shown to arise through increased expression of receptor tyrosine kinases such as EGFR; however, these changes decrease cell fitness and during a break from inhibitor treatment these cells are selected against, revealing that some patients who acquire EGFR expression may benefit from inhibitor re-treatment after a drug holiday.

Suggested Citation

  • Chong Sun & Liqin Wang & Sidong Huang & Guus J. J. E. Heynen & Anirudh Prahallad & Caroline Robert & John Haanen & Christian Blank & Jelle Wesseling & Stefan M. Willems & Davide Zecchin & Sebastijan H, 2014. "Reversible and adaptive resistance to BRAF(V600E) inhibition in melanoma," Nature, Nature, vol. 508(7494), pages 118-122, April.
    • Handle: RePEc:nat:nature:v:508:y:2014:i:7494:d:10.1038_nature13121
    DOI: 10.1038/nature13121
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    Citations

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    Cited by:

    1. Guillaume Harmange & Raúl A. Reyes Hueros & Dylan L. Schaff & Benjamin Emert & Michael Saint-Antoine & Laura C. Kim & Zijian Niu & Shivani Nellore & Mitchell E. Fane & Gretchen M. Alicea & Ashani T. W, 2023. "Disrupting cellular memory to overcome drug resistance," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Anastasia Samarkina & Markus Kirolos Youssef & Paola Ostano & Soumitra Ghosh & Min Ma & Beatrice Tassone & Tatiana Proust & Giovanna Chiorino & Mitchell P. Levesque & Sandro Goruppi & Gian Paolo Dotto, 2023. "Androgen receptor is a determinant of melanoma targeted drug resistance," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    3. Claudia Capparelli & Timothy J. Purwin & McKenna Glasheen & Signe Caksa & Manoela Tiago & Nicole Wilski & Danielle Pomante & Sheera Rosenbaum & Mai Q. Nguyen & Weijia Cai & Janusz Franco-Barraza & Ric, 2022. "Targeting SOX10-deficient cells to reduce the dormant-invasive phenotype state in melanoma," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    4. Thibault Houles & Geneviève Lavoie & Sami Nourreddine & Winnie Cheung & Éric Vaillancourt-Jean & Célia M. Guérin & Mathieu Bouttier & Benoit Grondin & Sichun Lin & Marc K. Saba-El-Leil & Stephane Ange, 2022. "CDK12 is hyperactivated and a synthetic-lethal target in BRAF-mutated melanoma," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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