With these chimeric E3s, we and others successfully rewired the oncoproteins such as Myc49, KRAS50, HER232, 42, EGFR33, 42, and IR/IGF-1R34 to ubiquitin-proteasome degradation route, and as a result, the oncogenes-related malignant behaviors of tumor cells as well as in vivo tumor growth were remarkably inhibited. The gene discussed is INSR; the disease is neoplasm.