Increased growth factor signaling, namely, epidermal growth factor (EGF) and insulin-like growth factor (IGF) signaling upstream of mTOR, has been observed frequently in NETs.[20] Also, insulin secretion is believed to be involved in the autocrine activation of mTOR in pancreatic beta cell tumors.[21] mTOR is activated by many gene mutations associated with NETs (germline deletion of the VHL gene).[12] mTOR directs the supply of nutrients to cancer cells by regulating angiogenesis. This evidence concerns the gene EGF and pancreatic insulin-producing neuroendocrine tumor.