This article reviews the identification of EGFR as a therapeutic target and the steps in the development of gefitinib as "targeted" monotherapy for patients with NSCLC.
Inhibition of the epidermal growth factor receptor (EGFR) with monoclonal antibodies or small-molecule inhibitors of the tyrosine kinase (TK) domain of the receptor have demonstrated modest, albeit significant, antitumor activities in patients with non-small-cell lung cancer (NSCLC).
Gefitinib (Iressa, ZD1839), an inhibitor of epidermal growth factor receptor-tyrosine kinase, has shown potent anti-tumor effects and improved symptoms and quality-of-life of a subset of patients with advanced non-small cell lung cancer (NSCLC).
Nonetheless, recent data revealed that non-small-cell lung cancer tumors that responded to single-agent Iressa possessed activating epidermal growth factor receptor mutations.
The NSCLC cell line PC-9 was seen to be hypersensitive to gefitinib and ZD6474, and a small (15-bp) in-frame deletion of an ATP-binding site (exon 19) in the EGFR was detected (delE746-A750-type deletion).
Thus, mutant EGFRs selectively transduce survival signals on which NSCLCs become dependent; inhibition of those signals by gefitinib may contribute to the drug's efficacy.
These new findings will undoubtedly lead to a greater understanding of the biology of EGFR-mutant NSCLC and the mechanism of action of EGFR TK inhibitors.
The successful application of dsRNA-EGFR for inhibition of proliferation in EGF receptor overexpressing cells can help extend the list of available therapeutic modalities in the treatment of non-small-cell lung carcinoma (NSCLC).
The epidermal growth factor receptor (EGFR) is commonly overexpressed in NSCLC, particularly squamous cell carcinoma, and has been implicated in the development and progression of this disease, although a clear correlation with prognosis has not been established.
High frequency of epidermal growth factor receptor mutations with complex patterns in non-small cell lung cancers related to gefitinib responsiveness in Taiwan.
We investigated the effect of EGFR antisense morpholino oligomer on non-small cell lung cancer (NSCLC) cell line by evaluating EGFR mRNA, protein product and cell proliferation.
"EGF receptor gene mutations are common in lung cancers from ""never smokers"" and are associated with sensitivity of tumors to gefitinib and erlotinib."
We searched for mutations in the EGFR gene in primary tumors from patients with non-small-cell lung cancer who had a response to gefitinib, those who did not have a response, and those who had not been exposed to gefitinib.
We report the first case showing that the status of EGFR mutations can be successfully determined in malignant pleural effusion of NSCLC using polymerase chain reaction (PCR) technique, and correlated to the clinical responsiveness to gefitinib, an EGFR-TKI.
We detected a total of 134 EGFR TK domain mutations in 130 (21%) of the 617 NSCLCs but not in any of the other carcinomas, nor in nonmalignant lung tissue from the same patients.