Addition of S-1 to the Epidermal Growth Factor Receptor Inhibitor Gefitinib Overcomes Gefitinib Resistance in Non–small cell Lung Cancer Cell Lines with MET Amplification

摘要: Purpose: Most non–small cell lung cancer (NSCLC) tumors with activating mutations in the epidermal growth factor receptor (EGFR) are initially responsive to EGFR tyrosine kinase inhibitors (EGFR-TKI) such as gefitinib and erlotinib, but they almost invariably develop resistance these drugs. A secondary mutation (T790M) amplification of MET proto-oncogene have been identified mechanisms acquired EGFR-TKIs. We now investigated whether addition oral fluoropyrimidine derivative S-1 might overcome NSCLC lines. Experimental Design: The effects on signaling expression both thymidylate synthase transcription E2F-1 gefitinib-resistant cells were examined by immunoblot analysis. (or 5-fluorouracil) vitro well nude mice. Results: Gefitinib induced down-regulation not those harboring T790M . combination 5-fluorouracil synergistically inhibited proliferation amplification, that EGFR, Similarly, only xenografts amplification. Conclusions: Our results suggest EGFR-TKIs is a promising strategy EGFR-TKI