In summary, adopting targeted approaches to characterize HCC lesions may make it possible to detect specific disease mechanisms, like for example AKT/mTOR, that can lead to: 1) develop biomarkers to support diagnosis and/or prognosis; 2) serve as targets for specific inhibitors rationally combined in individualized therapies to target case-specific mechanisms of hepatocyte transformation; and 3) design more effective combination therapies when used with sorafenib in advanced stages of HCC. This evidence concerns the gene AKT1 and hepatocellular carcinoma.