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Research Article

BIM Mediates EGFR Tyrosine Kinase Inhibitor-Induced Apoptosis in Lung Cancers with Oncogenic EGFR Mutations

  • Daniel B Costa,

    Affiliation: Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America

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  • Balázs Halmos,

    Affiliation: University Hospitals of Cleveland and Case Western Reserve University, Cleveland, Ohio, United States of America

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  • Amit Kumar,

    Affiliation: Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut, United States of America

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  • Susan T Schumer,

    Affiliation: Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America

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  • Mark S Huberman,

    Affiliation: Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America

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  • Titus J Boggon,

    Affiliation: Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut, United States of America

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  • Daniel G Tenen,

    Affiliation: Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America

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  • Susumu Kobayashi mail

    To whom correspondence should be addressed. E-mail: skobayas@bidmc.harvard.edu

    Affiliation: Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America

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  • Published: October 30, 2007
  • DOI: 10.1371/journal.pmed.0040315

About the Authors

Daniel B Costa, Susan T Schumer, Mark S Huberman, Daniel G Tenen, Susumu Kobayashi
Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America
Balázs Halmos
University Hospitals of Cleveland and Case Western Reserve University, Cleveland, Ohio, United States of America
Amit Kumar, Titus J Boggon
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut, United States of America

Corresponding Author

Email: skobayas@bidmc.harvard.edu

Competing Interests

The authors have declared that no competing interests exist.

Author Contributions

DBC conducted the experiments and analyzed the clinical and experimental data. AK and TJB generated the structural model of EGFR with secondary mutations and edited the manuscript. STS and MSH contributed to the clinical care, sample collection, and data acquisition of the gefitinib-resistant patients. BH and DGT supervised all aspects of this study including study design, execution, and interpretation. SK designed and conducted the experiments and analyzed the clinical and experimental data. DBC, BH, DGT and SK wrote the final manuscript.