This frequent occurrence of mutations in TP53, RB1 and PIK3CA is also typical of classic smoking-related SCLC [201] and was reported in previous cases of LACs transforming to SCLC following TKI-therapy, though the inactivation of the p53- and Rb1-signaling pathways more rarely may take place via other genetic/epigenetic mechanisms [68,192,193]. This evidence concerns the gene PIK3CA and small cell lung carcinoma.