EGFR and cancer: We found that TKI (gefitinib and erlotinib)-induced EGFR dimerization is dependent on palmitoylation and independent of kinase activity, mutations at cysteine residues known to be critical for EGFR’s palmitoylation abolished TKI-induced EGFR dimerization, TKI-induced EGFR dimerization is persistent in TKI-resistant cells, and inhibition of palmitoylation or targeted reduction of EGFR are lethal to TKI-resistant cancer cells.