For all three generations of EGFR TKIs, bypass activation of the insulin-like growth factor 1 receptor (IGF1R), which sustains the activation of the AKT and MAPK pathways, has been described as a mechanism of drug resistance in preclinical models of EGFR-mutated NSCLC [237,238,239,240,241,242,243]. The gene discussed is IGF1R; the disease is non-small cell lung carcinoma.