Overall, we demonstrate that suppressing β-catenin in CTNNB1-mutated tumors reprograms zone 3 tumors towards a zone 1/2 metabolic phenotype as early as 3-days post-LNP treatment, which contributes to the phenotypic differentiation and metabolic rewiring, loss of tumor nodules, and normalization of hepatic parenchyma and liver mass. The gene discussed is CTNNB1; the disease is neoplasm.