To address this grand challenge of ERBB2+ drug resistance in breast and lung cancer, we have developed an innovative approach based on genome engineering of the genetic codes on the 3’UTR (3’ untranslated region) of the ERBB2 gene to destabilize, overwrite/outcompete, and degrade ERBB2 transcript, protein expression, ERBB2-dependent kinases, and interactome. The gene discussed is ERBB2; the disease is lung carcinoma.