Regarding target alterations, some polymorphisms of the VEGFR2 gene have been correlated to reduced survival in HCC patients treated with sorafenib [39], whilst the increased activity of survival pathways such as MAPK/ERK, PI3K/AKT or Hedgehog has been associated with lower sensitivity to sorafenib in in vitro HCC models (36). This evidence concerns the gene KDR and hepatocellular carcinoma.