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The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers

Author

Listed:
  • Luis A. Diaz Jr

    (Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center
    Swim Across America Laboratory at Johns Hopkins)

  • Richard T. Williams

    (Amgen Inc.)

  • Jian Wu

    (Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center
    State Key Laboratory of Cancer Biology, The Fourth Military Medical University)

  • Isaac Kinde

    (Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center)

  • J. Randolph Hecht

    (David Geffen School of Medicine, University of California)

  • Jordan Berlin

    (Vanderbilt University Medical Center)

  • Benjamin Allen

    (Program for Evolutionary Dynamics, Harvard University)

  • Ivana Bozic

    (Program for Evolutionary Dynamics, Harvard University)

  • Johannes G. Reiter

    (Program for Evolutionary Dynamics, Harvard University
    IST Austria (Institute of Science and Technology Austria))

  • Martin A. Nowak

    (Program for Evolutionary Dynamics, Harvard University)

  • Kenneth W. Kinzler

    (Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center)

  • Kelly S. Oliner

    (Amgen Inc.)

  • Bert Vogelstein

    (Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center)

Abstract

This work on colorectal cancer shows that secondary mutations in KRAS that confer resistance to panitumumab, an anti-EGFR monoclonal antibody, are already present when antibody treatment begins; the apparent inevitability of resistance suggests that combinations of drugs targeting at least two different oncogenic pathway will be needed for treatment.

Suggested Citation

  • Luis A. Diaz Jr & Richard T. Williams & Jian Wu & Isaac Kinde & J. Randolph Hecht & Jordan Berlin & Benjamin Allen & Ivana Bozic & Johannes G. Reiter & Martin A. Nowak & Kenneth W. Kinzler & Kelly S. , 2012. "The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers," Nature, Nature, vol. 486(7404), pages 537-540, June.
    • Handle: RePEc:nat:nature:v:486:y:2012:i:7404:d:10.1038_nature11219
    DOI: 10.1038/nature11219
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    Cited by:

    1. Gaowei Fan & Kuo Zhang & Xin Yang & Jiansheng Ding & Zujian Wang & Jinming Li, 2017. "Prognostic value of circulating tumor DNA in patients with colon cancer: Systematic review," PLOS ONE, Public Library of Science, vol. 12(2), pages 1-17, February.

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