These findings indicate that cells or patients with CTNNB1 mutations may not respond to sorafenib because β-catenin activation is driven by the CTNNB1 mutation rather than solely by p-AKT or p-ERK, making PRI-724 crucial for synergistically inhibiting β-catenin nuclear translocation and activation in HCC with CTNNB1 mutation. Here, CTNNB1 is linked to hepatocellular carcinoma.