EGFR and non-small cell lung carcinoma: For EGFR TKIs, all of the above mechanisms of acquired resistance have been described clinically, including a secondary threonine-to-methionine substitution within the gatekeeper residue at position 790 (T790M), bypass signaling via amplification of the gene encoding the RTK MET to activate a parallel pathway, and phenotypic alterations either by an epithelial–mesenchymal transition, or even by a transformation from NSCLC to small-cell lung cancer (Sequist et al, 2011).