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.
Copyright 2005 Massachusetts Medical Society.
Publication types
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Case Reports
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Aged
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Antineoplastic Agents / adverse effects
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Antineoplastic Agents / therapeutic use*
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Biopsy
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Carcinoma, Non-Small-Cell Lung / diagnosis
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Carcinoma, Non-Small-Cell Lung / drug therapy
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Carcinoma, Non-Small-Cell Lung / genetics*
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DNA, Neoplasm
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Drug Resistance, Neoplasm / genetics*
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ErbB Receptors / antagonists & inhibitors*
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ErbB Receptors / chemistry
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ErbB Receptors / genetics*
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Erlotinib Hydrochloride
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Gefitinib
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Humans
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Lung Neoplasms / diagnosis
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Lung Neoplasms / drug therapy
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Lung Neoplasms / genetics*
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Male
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Models, Structural
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Molecular Structure
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Neoplasm Recurrence, Local / pathology
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Point Mutation
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Quinazolines / adverse effects
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Quinazolines / chemistry
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Quinazolines / metabolism
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Quinazolines / therapeutic use*
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RNA, Neoplasm
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Sequence Analysis, DNA
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Sequence Analysis, RNA
Substances
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Antineoplastic Agents
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DNA, Neoplasm
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Quinazolines
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RNA, Neoplasm
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Erlotinib Hydrochloride
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ErbB Receptors
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Gefitinib