PIK3CA and hepatocellular carcinoma: Although biomarkers that indicate the efficacy of mTOR inhibitors were validated in preclinical and clinical studies of various tumor types, for example, according to PIK3CA mutations, PTEN inactivation, and expression levels of p-S6, p-S6K, S6K, and p-AKT [33–35]; the validity of these markers was not confirmed in clinical trials, including those of patients with HCC [31].