Current evidence supports TP53 and RB1 mutations as potential predictors of phenotypic switch in EGFR-mutated NSCLC.[46] Moreover, a rapid increase in the serum levels of neuron-specific enolase (NSE), together with a poor response to EGFR-TKIs, usually indicates a transformation from adenocarcinoma to SCLC. This evidence concerns the gene TP53 and adenocarcinoma.