Back to Search
Start Over
Chronic nicotine exposure mediates resistance to EGFR-TKI in EGFR-mutated lung cancer via an EGFR signal.
- Source :
-
Lung Cancer (01695002) . Apr2015, Vol. 88 Issue 1, p16-23. 8p. - Publication Year :
- 2015
-
Abstract
- Background Some of patients with non-small cell lung cancer (NSCLC) harboring somatic activating mutations of the epidermal growth factor receptor gene ( EGFR mutations) show poor responses to EGFR-tyrosine kinase inhibitors (EGFR-TKIs) treatment. Cigarette smoking is the strongest documented risk factor for the development of lung cancer. Nicotine, while not carcinogenic by itself, has been shown to induce proliferation, angiogenesis, and the epithelial-mesenchymal transition; these effects might be associated with EGFR-TKI resistance. Materials and methods PC-9 and 11_18 cell lines ( EGFR -mutated NSCLC cell lines) were cultured with 1 μM nicotine for 3 months and were designated as PC-9/N and 11_18/N cell lines, respectively. The sensitivities of these cell lines to EGFR-TKI were then tested in vitro . Moreover, the association between the smoking status and the progression-free survival (PFS) period was investigated in patients with EGFR -mutated NSCLC who were treated with gefitinib. Results The PC-9/N and 11_18/N cell lines were resistant to EGFR-TKI, compared with controls. The phosphorylation of EGFR in these cell lines was reduced by EGFR-TKI to a smaller extent than that observed in controls, and a higher concentration of EGFR-TKI was capable of further decreasing the phosphorylation. Clinically, smoking history was an independent predictor of a poor PFS period on gefitinib treatment. Conclusions Chronic nicotine exposure because of cigarette smoking mediates resistance to EGFR-TKI via an EGFR signal. Smoking cessation is of great importance, while resistance may be overcome through the administration of high-dose EGFR-TKI. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01695002
- Volume :
- 88
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Lung Cancer (01695002)
- Publication Type :
- Academic Journal
- Accession number :
- 101411655
- Full Text :
- https://doi.org/10.1016/j.lungcan.2015.01.027