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Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation

Author

Listed:
  • Ramin Nazarian

    (UCLA’s Jonsson Comprehensive Cancer Center, 52-121 CHS, Los Angeles, California 90095-1750, USA
    David Geffen School of Medicine, University of California)

  • Hubing Shi

    (UCLA’s Jonsson Comprehensive Cancer Center, 52-121 CHS, Los Angeles, California 90095-1750, USA
    David Geffen School of Medicine, University of California)

  • Qi Wang

    (UCLA’s Jonsson Comprehensive Cancer Center, 52-121 CHS, Los Angeles, California 90095-1750, USA
    David Geffen School of Medicine, University of California)

  • Xiangju Kong

    (UCLA’s Jonsson Comprehensive Cancer Center, 52-121 CHS, Los Angeles, California 90095-1750, USA
    David Geffen School of Medicine, University of California)

  • Richard C. Koya

    (David Geffen School of Medicine, University of California
    UCLA’s Jonsson Comprehensive Cancer Center, 54-140 CHS, Los Angeles, California 90095-1782, USA)

  • Hane Lee

    (David Geffen School of Medicine, University of California
    UCLA’s Jonsson Comprehensive Cancer Center, 5506A Gonda Center)

  • Zugen Chen

    (David Geffen School of Medicine, University of California
    UCLA’s Jonsson Comprehensive Cancer Center, 5506A Gonda Center)

  • Mi-Kyung Lee

    (UCLA’s Jonsson Comprehensive Cancer Center, 52-121 CHS, Los Angeles, California 90095-1750, USA
    David Geffen School of Medicine, University of California)

  • Narsis Attar

    (David Geffen School of Medicine, University of California
    UCLA’s Jonsson Comprehensive Cancer Center, 9-954 Factor Building, Los Angeles, California 90095-1678, USA)

  • Hooman Sazegar

    (David Geffen School of Medicine, University of California
    UCLA’s Jonsson Comprehensive Cancer Center, 9-954 Factor Building, Los Angeles, California 90095-1678, USA)

  • Thinle Chodon

    (David Geffen School of Medicine, University of California
    UCLA’s Jonsson Comprehensive Cancer Center, 9-954 Factor Building, Los Angeles, California 90095-1678, USA)

  • Stanley F. Nelson

    (David Geffen School of Medicine, University of California
    UCLA’s Jonsson Comprehensive Cancer Center, 5506A Gonda Center
    UCLA’s Jonsson Comprehensive Cancer Center, 5506A Gonda Center)

  • Grant McArthur

    (Peter MacCallum Cancer Center)

  • Jeffrey A. Sosman

    (Vanderbilt-Ingram Cancer Center, 777 Preston Research Building, Nashville, Tennessee 37232-6838, USA)

  • Antoni Ribas

    (David Geffen School of Medicine, University of California
    UCLA’s Jonsson Comprehensive Cancer Center, 54-140 CHS, Los Angeles, California 90095-1782, USA
    UCLA’s Jonsson Comprehensive Cancer Center, 9-954 Factor Building, Los Angeles, California 90095-1678, USA)

  • Roger S. Lo

    (UCLA’s Jonsson Comprehensive Cancer Center, 52-121 CHS, Los Angeles, California 90095-1750, USA
    David Geffen School of Medicine, University of California)

Abstract

Drug-resistance mechanism in melanoma Clinical trials in melanoma patients carrying B-RAF gene mutations have shown promising results with the B-RAF kinase inhibitor PLX4032, but many patients go on to become resistant. Two papers now uncover possible mechanisms for this resistance. Nazarian et al. report that melanomas can acquire resistance due to mutations of N-RAS or increased expression of PDGFRβ, and Johannessen et al. report resistance due to upregulation of MAP3K8/COT. Each of these mechanisms seems to apply to some patients in the recent PLX4032 trial, yet surprisingly, no secondary B-RAF mutations were observed.

Suggested Citation

  • Ramin Nazarian & Hubing Shi & Qi Wang & Xiangju Kong & Richard C. Koya & Hane Lee & Zugen Chen & Mi-Kyung Lee & Narsis Attar & Hooman Sazegar & Thinle Chodon & Stanley F. Nelson & Grant McArthur & Jef, 2010. "Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation," Nature, Nature, vol. 468(7326), pages 973-977, December.
    • Handle: RePEc:nat:nature:v:468:y:2010:i:7326:d:10.1038_nature09626
    DOI: 10.1038/nature09626
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    Cited by:

    1. Zhang Liqun, 2022. "The Influence of Entrepreneur's Social Capital and Resource Acquisition on Enterprise's Innovation Ability -- A Case Study of Guangdong Entrepreneurs," International Journal of Science and Business, IJSAB International, vol. 14(1), pages 130-154.

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