AKT1 and hepatocellular carcinoma: Several explanations have been proposed for the limited efficacy in earlier trials: (i) the low prevalence of canonical sensitizing EGFR mutations in HCC (24); (ii) intratumoral heterogeneity and clonal diversity, which limit drug efficacy (25, 26); and (iii) compensatory activation of parallel signaling pathways such as PI3K/AKT and MAPK/ERK (27, 28).