Firstly, the activation of intrinsic RIG-I and MDA-5 in tumor cells can directly induce cell apoptosis, independent of type I IFNs.489–491 Significantly, RIG-I-mediated apoptosis is observed predominantly in tumor cells, while non-malignant cells are shielded from this pro-apoptotic signaling through the expression of Bcl-xL.491 This selective action underscores the therapeutic potential of targeting RIG-I in cancer treatment, as it may offer a safety margin by sparing normal cells from apoptotic induction. This evidence concerns the gene IFIH1 and cancer.