Conversely, following treatment with EGFR-TKI, the resistant pluripotent cells, which may have accumulated additional genetic alterations (such as loss of RB1 and TP53) and maintain a different epigenetic state, are able to differentiate and subsequently expand along a lineage (SCLC) that does not require EGFR signalling (Supplementary Fig. 7, right panel). This evidence concerns the gene RB1 and small cell lung carcinoma.