RB1 and small cell lung carcinoma: One reason for the slow development of gene-oriented therapeutic approaches is that if there are non-small-cell lung cancer cases with driver oncogenic-activating genetic events (such as in the EGFR, ALK, and ROS genes) [40], small-cell lung cancer exhibits mostly loss-of-function events in its pathogenesis (such as mutations in the tumor suppressor genes RB1 or TP53).