Somatic mutations of the epidermal growth factor receptor and non-small-cell lung cancer.
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.
Zhang
Xiaozhu
X
Division of Biomedical Sciences, Johns Hopkins Singapore, 31 Biopolis Way, #02-01, the Nanos, Singapore 138669, Singapore. xiaozhu@imc.jhmi.edu
Chang
Alex
A
D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D017322:Clinical Trials, Phase II as Topic; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D004311:Double-Blind Method; D016503:Drug Delivery Systems; D015195:Drug Design; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000502:physiology*; D005006:Ethnicity / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D000077156:Gefitinib; D018773:Genes, erbB-1; D016158:Genes, p53; D011905:Genes, ras; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D008297:Male; D016254:Mutagenesis, Insertional; D009154:Mutation; D020125:Mutation, Missense; D017434:Protein Structure, Tertiary / Q000235:genetics; D011799:Quinazolines / Q000494:pharmacology / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D017384:Sequence Deletion; D012907:Smoking
D004273:DNA, Neoplasm; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib