During targeted therapy, most patients carrying the driver genetic alterations (e.g., EGFR mutations in non-small cell lung cancer (NSCLC) and fusion protein BCR/ABL in CML) would respond to corresponding targeted agents thus be benefited, while some patients do not respond well and thus are considered to experience primary or intrinsic resistance. The gene discussed is EGFR; the disease is non-small cell lung carcinoma.