Together, these findings raise the intriguing possibility that elevated KSR1 expression may function as a tumor suppressive mechanism in cancers harboring constitutively active RAS or RAF mutations by driving RAS/MAPK signaling into a state of toxic hyperactivation, whereas in tumors lacking such mutations (e.g., HCC, ccRCC), increased KSR1 levels instead enhance oncogenic signaling and promote tumorigenesis. This evidence concerns the gene RAF1 and hepatocellular carcinoma.