With our new strategy of targeting SINA/SIAH1/SIAH2, the most conserved and the most downstream “signaling gatekeeper” identified thus far in the RAS signaling pathway, we aim to bypass obstacles such as the extensive bifurcation, cross-talk and dynamic feedback controls downstream of several major compensatory K-RAS effector pathways to impede and block oncogenic K-RAS-driven malignant tumors [10]. This evidence concerns the gene SIAH1 and cancer.