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Research Article

Acquired Resistance of Lung Adenocarcinomas to Gefitinib or Erlotinib Is Associated with a Second Mutation in the EGFR Kinase Domain

  • William Pao equal contributor mail,

    equal contributor Contributed equally to this work with: William Pao, Vincent A Miller

    To whom correspondence should be addressed. E-mail: paow@mskcc.org

    Affiliations: Program in Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America, Thoracic Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America

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  • Vincent A Miller equal contributor,

    equal contributor Contributed equally to this work with: William Pao, Vincent A Miller

    Affiliation: Thoracic Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America

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  • Katerina A Politi,

    Affiliation: Program in Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America

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  • Gregory J Riely,

    Affiliation: Thoracic Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America

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  • Romel Somwar,

    Affiliation: Program in Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America

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  • Maureen F Zakowski,

    Affiliation: Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America

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  • Mark G Kris,

    Affiliation: Thoracic Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America

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  • Harold Varmus

    Affiliation: Program in Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America

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  • Published: February 22, 2005
  • DOI: 10.1371/journal.pmed.0020073

About the Authors

William Pao, Katerina A Politi, Romel Somwar, Harold Varmus
Program in Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America
William Pao, Vincent A Miller, Gregory J Riely, Mark G Kris
Thoracic Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America
Maureen F Zakowski
Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America

Corresponding Author

Email: paow@mskcc.org

Competing Interests

VAM has received research funding from Genentech (co-developer of erlotinib) and has received honoraria from AstraZeneca (maker of gefitinib) for consultancy. MGK has received research funding from AstraZeneca and research funding and consulting fees from Genentech and has represented AstraZeneca before the United States Food and Drug Administration. WP, VAM, MFZ, and HV, represented by the Sloan-Kettering Institute for Cancer Research, filed on June 1, 2004, a provisional patent application entitled “Use of mutations in EGFR kinase as an indicator of therapeutic efficacy of erlotinib in the treatment of NSCLC,” patent 60/576,275. HV is Co-founder and Chair of the Board of Directors of the Public Library of Science.

Author Contributions

WP conceived and designed the study; acquired, analyzed, and interpreted the data; and drafted the article and revised the manuscript. VAM conceived and designed the clinical aspects of the study, analyzed and interpreted the data, and helped draft the article. KAP helped design aspects of the study; acquired, analyzed, and interpreted the data; and helped draft the article. GJR helped acquire the clinical data and specimens and critically read the manuscript. RS designed and performed the cell viability studies and critically read the manuscript. MFZ acquired the pathologic data and critically read the manuscript. MGK helped acquire the clinical data and specimens and critically read the manuscript. HV contributed to the conception and design of the study and to the interpretation of the data, and edited the article and the revised manuscript.