INS and cancer: Several important signaling pathways, including PI3K/Akt/FRAP, Raf/MEK/p42/p44 MAPK, and JAK/Stat, and their downstream transcription factor targets, such as HIF-1, Sp1, AP-1, and Stat3, play a critical role in the induction of VEGF-A by growth factors (IGF1, PDGF, EGF, and FGF), hormones (prostaglandin E2 and insulin), and cytokines (IL-1β, IL-6, and IL-8) in cancer cells [38, 39].