Drug combination approach to overcome resistance to EGFR tyrosine kinase inhibitors in lung cancer

The discovery of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) has led to unprecedented clinical response in a subset of lung cancer patients carrying the sensitizing EGFR mutations (L858R or exon 19 deletion). However, disease progression invariably occurs within a year after the initial TKI treatment, predominantly due to the development of acquired resistance caused by the secondary EGFR T790M mutation. Numerous second generation irreversible and third generation EGFR T790M selective EGFR TKIs have been developed to overcome resistance.

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