As epigenetic regulation is usually not involved in gene mutation and amplification, which are regarded as the main causes of EGFR-TKI resistance in NSCLC5, we presumed that activation of bypass pathways, including the AKT, NF-κB, WNT, Hedgehog, and YAP pathways, which were reported to affect EGFR-TKI resistance by self-activation15–19, may be associated with EHMT2-mediated EGFR-TKI resistance in NSCLC cells. The gene discussed is EGFR; the disease is non-small cell lung carcinoma.