IGF1 and Other metabolic disease: IGF-1R is overexpressed in vitro and in animal models of HCC [26,36,37], suggesting that activation of the IGF/IGF-1R axis and its related signaling pathways, such as the PI3K/Akt signaling pathway, significantly contribute to the stimulation of HCC cell growth and liver carcinogenesis, especially in the presence of metabolic disorders.