RB1 and neoplasm: Conversely, in other patients, tumor progression in association with the LAC-to-SCLC transformation is observed just a few weeks after initiating EGFR-TKIs [68,195] and SCLC clones are detectable before TKI-treatment in LACs with TP53 and RB1 inactivation, thereby justifying the inclusion of this phenotypic change among the possible mechanisms of intrinsic TKI-resistance.