Novel epidermal growth factor receptor inhibitor accumulates in the brain and inhibits the growth of brain metastatic non-small cell lung cancer

mesenchymal markers, vimentin and N-cadherin in STM cells. Enhanced invasion and migration capabilities were observed in STM cells consistent with a mesenchymal phenotype. Src has been shown to play a role in E-cadherin regulation and EMT. Thus, treatment of cells with dasatinib, a Src inhibitor, suppressed cell growth in STM cells, but not in ALKþ/TKI sensitive cell lines. The addition of a low dose of dasatinib sensitized STM cells to the antiproliferative effects of crizotinib. STMcellswere subjected to genetic analysis to identify new genetic anomalies that could be driving resistance. Top hits are being evaluated. To our knowledge, this is the first report that demonstrates EMT occurring in an ALKþ crizotinib resistant clinical sample. Collectively these data support EMT as a mechanism of resistance to crizotinib and identifies dasatinib as a potential therapeutic for treatment of crizotinib resistance associated with EMT.