Analyses of the underlying molecular mechanisms have revealed that abnormal phosphorylation modifications (EGFR, ERK, AKT, and STAT-3), the epithelial-to-mesenchymal transition (EMT), CSC properties, and angiogenesis enhancement are involved in the resistance of HCC cells to sorafenib, while the heterogeneity of tumor vessels (lack of VEFGR1/2) and the advancement of hepatic fibrosis, as well as inflammation and hypoxia, contribute to microenvironmental or vascular resistance29–31. The gene discussed is STAT3; the disease is neoplasm.