INSR and Insulin resistance: First, insulin resistance and hyperinsulinemia, with insulin and insulin-like growth factor-1 (IGF-1) binding to the IR/IGF1R receptor, are triggered via the insulin receptor substrate 1 (IRS-1) signaling cascade through PI3K and MAPK pathways, with cell proliferation induction and apoptosis inhibition being main factors in HCC pathogenesis [54,55,56].