In this regard, genomic alterations such as the EGFR T790M mutation; the activation of bypass signaling pathways, including RAS/ERK, PIK3/AKT, and MET alterations; the histological transformation into small-cell lung cancer (SCLC); and the acquisition of the epithelial–mesenchymal transition (EMT) phenotype are the main mechanisms responsible for biological resistance to EGFR-TKIs [3,4]. This evidence concerns the gene PIK3CG and small cell lung carcinoma.