Here, we studied whether the EMT phenomenon that drives acquired resistance to first-generation ALK–TKI therapy suffices to promote cross-resistance to new-generation ALK–TKIs and whether the known anti-EMT [37,38,39,40]/anti-TGFβ [41,42,43,44] signaling activity of the flavonolignan silibinin could be exploited to re-sensitize drug-refractory mesenchymal NSCLC cells to ALK–TKIs, and explored the mechanisms involved. The gene discussed is TGFB1; the disease is non-small cell lung carcinoma.