We demonstrated that ligands of MET (HGF) and EGFR (EGF, HB-EGF, and TGF-α) triggered resistance to alectinib in ALK-rearranged NSCLC cells, and that the Hsp90 inhibitor 17-DMAG overcame the resistance triggered by these receptor ligands. The gene discussed is HBEGF; the disease is non-small cell lung carcinoma.