INS and neoplasm: Both insulin/insulin receptor and IGF signaling pathways lead to the activation of insulin response substrate-1 (IRS-1) and the receptor tyrosine kinase pathway, including Ras/Raf/MAPK kinase/extracellular signal-regulated kinase (ERK) cascade, which is essential for carcinogenesis by promoting the proliferation and protein synthesis and inhibiting apoptosis of tumor cells (68, 69).