Although the mechanisms by which SCLC-transformation leads to TKI-resistance need to be addressed more specifically, it is also fair to speculate that the TP53-, RB1-, and PIK3CA-mutations identified in the transformed tumors may contribute to TKI-resistance, given that these genes regulate a multitude of mechanisms implicated in cell proliferation and survival downstream EGFR. This evidence concerns the gene RB1 and small cell lung carcinoma.