Clinically, emergence of TKI-resistant EGFR mutant LUADs that exhibit small cell lung cancer (SCLC) lineage markers and heralded by RB1 and TP53 loss (Fig. 2) has been observed as another example of a reprogramming response [18, 57–59], although this seems to be a late event in the course of therapy [58]. Here, EGFR is linked to small cell lung carcinoma.