In addition to the acquisition of EGFR mutations, such as T790 M (resistance to gefitinib, erlotinib and ecotinib) [11] and C797S (resistance to osimertinib) [12], the activation of receptor tyrosine kinases (RTKs) combined with triggering downstream signaling pathways, including RAS and mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K) and Akt, or signal transducer and activator of transcription 3 (STAT3), has been recognized to drive EGFR-TKI resistance in lung cancer [13]. The gene discussed is STAT3; the disease is lung carcinoma.