The ERBB network facilitates KRAS-driven lung tumorigenesis

    Research output: Contribution to journalArticle

    Published

    Standard

    The ERBB network facilitates KRAS-driven lung tumorigenesis. / Kruspig, Björn; Monteverde, Tiziana; Neidler, Sarah; Hock, Andreas; Kerr, Emma; Nixon, Colin; Clark, William; Hedley, Ann; Laing, Sarah; Coffelt, Seth B; Le Quesne, John; Dick, Craig; Vousden, Karen; Martins, Carla P; Murphy, Daniel J.

    In: Science Translational Medicine, Vol. 10, No. 446, 20.06.2018.

    Research output: Contribution to journalArticle

    Harvard

    Kruspig, B, Monteverde, T, Neidler, S, Hock, A, Kerr, E, Nixon, C, Clark, W, Hedley, A, Laing, S, Coffelt, SB, Le Quesne, J, Dick, C, Vousden, K, Martins, CP & Murphy, DJ 2018, 'The ERBB network facilitates KRAS-driven lung tumorigenesis', Science Translational Medicine, vol. 10, no. 446. https://doi.org/10.1126/scitranslmed.aao2565

    APA

    Kruspig, B., Monteverde, T., Neidler, S., Hock, A., Kerr, E., Nixon, C., ... Murphy, D. J. (2018). The ERBB network facilitates KRAS-driven lung tumorigenesis. Science Translational Medicine, 10(446). https://doi.org/10.1126/scitranslmed.aao2565

    Vancouver

    Author

    Kruspig, Björn ; Monteverde, Tiziana ; Neidler, Sarah ; Hock, Andreas ; Kerr, Emma ; Nixon, Colin ; Clark, William ; Hedley, Ann ; Laing, Sarah ; Coffelt, Seth B ; Le Quesne, John ; Dick, Craig ; Vousden, Karen ; Martins, Carla P ; Murphy, Daniel J. / The ERBB network facilitates KRAS-driven lung tumorigenesis. In: Science Translational Medicine. 2018 ; Vol. 10, No. 446.

    Bibtex

    @article{1f13dae9df624bb59564e33482228197,
    title = "The ERBB network facilitates KRAS-driven lung tumorigenesis",
    abstract = "KRAS is the most frequently mutated driver oncogene in human adenocarcinoma of the lung. There are presently no clinically proven strategies for treatment of KRAS-driven lung cancer. Activating mutations in KRAS are thought to confer independence from upstream signaling; however, recent data suggest that this independence may not be absolute. We show that initiation and progression of KRAS-driven lung tumors require input from ERBB family receptor tyrosine kinases (RTKs): Multiple ERBB RTKs are expressed and active from the earliest stages of KRAS-driven lung tumor development, and treatment with a multi-ERBB inhibitor suppresses formation of KRASG12D-driven lung tumors. We present evidence that ERBB activity amplifies signaling through the core RAS pathway, supporting proliferation of KRAS-mutant tumor cells in culture and progression to invasive disease in vivo. Brief pharmacological inhibition of the ERBB network enhances the therapeutic benefit of MEK (mitogen-activated protein kinase kinase) inhibition in an autochthonous tumor setting. Our data suggest that lung cancer patients with KRAS-driven disease may benefit from inclusion of multi-ERBB inhibitors in rationally designed treatment strategies.",
    author = "Bj{\"o}rn Kruspig and Tiziana Monteverde and Sarah Neidler and Andreas Hock and Emma Kerr and Colin Nixon and William Clark and Ann Hedley and Sarah Laing and Coffelt, {Seth B} and {Le Quesne}, John and Craig Dick and Karen Vousden and Martins, {Carla P} and Murphy, {Daniel J}",
    note = "Copyright {\circledC} 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.",
    year = "2018",
    month = "6",
    day = "20",
    doi = "10.1126/scitranslmed.aao2565",
    language = "English",
    volume = "10",
    journal = "Science Translational Medicine",
    issn = "1946-6234",
    publisher = "American Association for the Advancement of Science",
    number = "446",

    }

    RIS

    TY - JOUR

    T1 - The ERBB network facilitates KRAS-driven lung tumorigenesis

    AU - Kruspig, Björn

    AU - Monteverde, Tiziana

    AU - Neidler, Sarah

    AU - Hock, Andreas

    AU - Kerr, Emma

    AU - Nixon, Colin

    AU - Clark, William

    AU - Hedley, Ann

    AU - Laing, Sarah

    AU - Coffelt, Seth B

    AU - Le Quesne, John

    AU - Dick, Craig

    AU - Vousden, Karen

    AU - Martins, Carla P

    AU - Murphy, Daniel J

    N1 - Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

    PY - 2018/6/20

    Y1 - 2018/6/20

    N2 - KRAS is the most frequently mutated driver oncogene in human adenocarcinoma of the lung. There are presently no clinically proven strategies for treatment of KRAS-driven lung cancer. Activating mutations in KRAS are thought to confer independence from upstream signaling; however, recent data suggest that this independence may not be absolute. We show that initiation and progression of KRAS-driven lung tumors require input from ERBB family receptor tyrosine kinases (RTKs): Multiple ERBB RTKs are expressed and active from the earliest stages of KRAS-driven lung tumor development, and treatment with a multi-ERBB inhibitor suppresses formation of KRASG12D-driven lung tumors. We present evidence that ERBB activity amplifies signaling through the core RAS pathway, supporting proliferation of KRAS-mutant tumor cells in culture and progression to invasive disease in vivo. Brief pharmacological inhibition of the ERBB network enhances the therapeutic benefit of MEK (mitogen-activated protein kinase kinase) inhibition in an autochthonous tumor setting. Our data suggest that lung cancer patients with KRAS-driven disease may benefit from inclusion of multi-ERBB inhibitors in rationally designed treatment strategies.

    AB - KRAS is the most frequently mutated driver oncogene in human adenocarcinoma of the lung. There are presently no clinically proven strategies for treatment of KRAS-driven lung cancer. Activating mutations in KRAS are thought to confer independence from upstream signaling; however, recent data suggest that this independence may not be absolute. We show that initiation and progression of KRAS-driven lung tumors require input from ERBB family receptor tyrosine kinases (RTKs): Multiple ERBB RTKs are expressed and active from the earliest stages of KRAS-driven lung tumor development, and treatment with a multi-ERBB inhibitor suppresses formation of KRASG12D-driven lung tumors. We present evidence that ERBB activity amplifies signaling through the core RAS pathway, supporting proliferation of KRAS-mutant tumor cells in culture and progression to invasive disease in vivo. Brief pharmacological inhibition of the ERBB network enhances the therapeutic benefit of MEK (mitogen-activated protein kinase kinase) inhibition in an autochthonous tumor setting. Our data suggest that lung cancer patients with KRAS-driven disease may benefit from inclusion of multi-ERBB inhibitors in rationally designed treatment strategies.

    U2 - 10.1126/scitranslmed.aao2565

    DO - 10.1126/scitranslmed.aao2565

    M3 - Article

    VL - 10

    JO - Science Translational Medicine

    T2 - Science Translational Medicine

    JF - Science Translational Medicine

    SN - 1946-6234

    IS - 446

    ER -

    Download

    Download as: RIS