Abstract
Frequent overexpression of epidermal growth factor receptor (EGFR) in non-small-cell lung cancer (NSCLC) makes EGFR a new therapeutic target. Two specific EGFR tyrosine kinase inhibitors, gefitinib (ZD1839, Iressa) and erlotinib (OSI-774, Tarceva), have been developed and approved by the US Food and Drug Administration for second-line and third-line treatment of advanced NSCLC. Clinical trials have shown considerable variability in the response rate between different patients with NSCLC, which led to the discovery of somatic EGFR-activating mutations. This brief review summarises the discovery and functional consequences of the mutations, their clinicopathological features and significant implications in the treatment and prognosis of NSCLC.
MeSH terms
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Adenocarcinoma / drug therapy
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Adenocarcinoma / enzymology
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Adenocarcinoma / genetics
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Carcinoma, Non-Small-Cell Lung / drug therapy
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Carcinoma, Non-Small-Cell Lung / enzymology
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Carcinoma, Non-Small-Cell Lung / genetics*
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Cell Transformation, Neoplastic / genetics
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Clinical Trials, Phase II as Topic
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DNA Mutational Analysis
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DNA, Neoplasm / genetics
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Double-Blind Method
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Drug Delivery Systems
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Drug Design
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Drug Resistance, Neoplasm
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ErbB Receptors / antagonists & inhibitors
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ErbB Receptors / physiology*
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Ethnicity / genetics
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Exons / genetics
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Female
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Gefitinib
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Genes, erbB-1*
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Genes, p53
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Genes, ras
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Genotype
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Humans
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Lung Neoplasms / drug therapy
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Lung Neoplasms / enzymology
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Lung Neoplasms / genetics*
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Male
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Mutagenesis, Insertional
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Mutation*
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Mutation, Missense
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Protein Structure, Tertiary / genetics
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Quinazolines / pharmacology
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Quinazolines / therapeutic use
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Randomized Controlled Trials as Topic
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Sequence Deletion
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Smoking
Substances
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DNA, Neoplasm
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Quinazolines
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ErbB Receptors
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Gefitinib