Marcoux et al. reported that 19 patients with NSCLC developed SCLC transformation after third-generation EGFR-TKI treatment, and this change was characterized by Rb1, TP53, and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations [98]. This evidence concerns the gene PIK3CA and non-small cell lung carcinoma.