Taken together, the findings demonstrate that the novel engineered destabilized 3’UTR of ERBB2 effectively degraded the ERBB2 transcript and protein expression to kill cancer cells in a clinically relevant model of ERBB2+-overexpressing osimertinib-resistant EGFR T790M non-small-cell lung cancer, in ERBB2-mutated non-small-cell lung cancer, in ERBB2+-expressing colorectal cancer cell line, in difficult-to-treat ERBB2+ trastuzumab-resistant breast cancer cell line, and in wildtype ERBB2+-expressing breast cancer. This evidence concerns the gene EGFR and non-small cell lung carcinoma.