EGFR mutation and resistance of non-small-cell lung cancer to gefitinib

Susumu Kobayashi; Titus J. Boggon; Tajhal Dayaram; Pasi A. Jänne; Olivier Kocher; Matthew Meyerson; Bruce E. Johnson; Michael J. Eck; Daniel G. Tenen; Balázs Halmos

doi:10.1056/NEJMoa044238

EGFR mutation and resistance of non-small-cell lung cancer to gefitinib

Susumu Kobayashi, Titus J. Boggon, Tajhal Dayaram, Pasi A. Jänne, Olivier Kocher, Matthew Meyerson, Bruce E. Johnson, Michael J. Eck, Daniel G. Tenen, Balázs Halmos

Research output: Contribution to journal › Article › peer-review

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Abstract

Mutations of the epidermal growth factor receptor (EGFR) gene have been identified in specimens from patients with non-small-cell lung cancer who have a response to anilinoquinazoline EGFR inhibitors. Despite the dramatic responses to such inhibitors, most patients ultimately have a relapse. The mechanism of the drug resistance is unknown. Here we report the case of a patient with EGFR-mutant, gefitinib-responsive, advanced non-small-cell lung cancer who had a relapse after two years of complete remission during treatment with gefitinib. The DNA sequence of the EGFR gene in his tumor biopsy specimen at relapse revealed the presence of a second point mutation, resulting in threonine-to-methionine amino acid change at position 790 of EGFR. Structural modeling and biochemical studies showed that this second mutation led to gefitinib resistance.

Original language	English (US)
Pages (from-to)	786-792
Number of pages	7
Journal	New England Journal of Medicine
Volume	352
Issue number	8
DOIs	https://doi.org/10.1056/NEJMoa044238
State	Published - Feb 24 2005
Externally published	Yes

ASJC Scopus subject areas

General Medicine

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1056/NEJMoa044238

Cite this

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title = "EGFR mutation and resistance of non-small-cell lung cancer to gefitinib",

abstract = "Mutations of the epidermal growth factor receptor (EGFR) gene have been identified in specimens from patients with non-small-cell lung cancer who have a response to anilinoquinazoline EGFR inhibitors. Despite the dramatic responses to such inhibitors, most patients ultimately have a relapse. The mechanism of the drug resistance is unknown. Here we report the case of a patient with EGFR-mutant, gefitinib-responsive, advanced non-small-cell lung cancer who had a relapse after two years of complete remission during treatment with gefitinib. The DNA sequence of the EGFR gene in his tumor biopsy specimen at relapse revealed the presence of a second point mutation, resulting in threonine-to-methionine amino acid change at position 790 of EGFR. Structural modeling and biochemical studies showed that this second mutation led to gefitinib resistance.",

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AU - Kobayashi, Susumu

AU - Boggon, Titus J.

AU - Dayaram, Tajhal

AU - Jänne, Pasi A.

AU - Kocher, Olivier

AU - Meyerson, Matthew

AU - Johnson, Bruce E.

AU - Eck, Michael J.

AU - Tenen, Daniel G.

AU - Halmos, Balázs

PY - 2005/2/24

Y1 - 2005/2/24

N2 - Mutations of the epidermal growth factor receptor (EGFR) gene have been identified in specimens from patients with non-small-cell lung cancer who have a response to anilinoquinazoline EGFR inhibitors. Despite the dramatic responses to such inhibitors, most patients ultimately have a relapse. The mechanism of the drug resistance is unknown. Here we report the case of a patient with EGFR-mutant, gefitinib-responsive, advanced non-small-cell lung cancer who had a relapse after two years of complete remission during treatment with gefitinib. The DNA sequence of the EGFR gene in his tumor biopsy specimen at relapse revealed the presence of a second point mutation, resulting in threonine-to-methionine amino acid change at position 790 of EGFR. Structural modeling and biochemical studies showed that this second mutation led to gefitinib resistance.

AB - Mutations of the epidermal growth factor receptor (EGFR) gene have been identified in specimens from patients with non-small-cell lung cancer who have a response to anilinoquinazoline EGFR inhibitors. Despite the dramatic responses to such inhibitors, most patients ultimately have a relapse. The mechanism of the drug resistance is unknown. Here we report the case of a patient with EGFR-mutant, gefitinib-responsive, advanced non-small-cell lung cancer who had a relapse after two years of complete remission during treatment with gefitinib. The DNA sequence of the EGFR gene in his tumor biopsy specimen at relapse revealed the presence of a second point mutation, resulting in threonine-to-methionine amino acid change at position 790 of EGFR. Structural modeling and biochemical studies showed that this second mutation led to gefitinib resistance.

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EGFR mutation and resistance of non-small-cell lung cancer to gefitinib

Abstract

ASJC Scopus subject areas

UN SDGs

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