Flunarizine, originally indicated for migraineprophylaxis and vertigo treatment, was selected for detailed investigationin NSCLC cell lines harboring a range of different gefitinib resistancemechanisms (EGFR T790M, KRAS G12S, MET amplification, or PTEN loss).The circumvention of gefitinib resistance by flunarizine was furtherdemonstrated in an EGFR TKI (erlotinib)-refractory patient-derivedtumor xenograft (PDX) model in vivo. This evidence concerns the gene KRAS and non-small cell lung carcinoma.