Figure 3: Schematic representation of the two major signaling cascades operating in cancer, following overactivation of the INSR/IGF-IR signaling pathways. Binding of insulin, IGF-I (and IGF-II) triggers the intrinsic tyrosine kinase receptor domain, leading to activation of the PI3K/Akt/mTOR signaling and the MAP/ERK-kinase pathway. HR: hybrid receptors; ERK: extracellular regulated kinase; IRS: INSR substrate; MEK: mitogen-activated protein kinase kinase; mTOR: mammalian target of rapamycin; PI3K: Phosphoinositide-3 kinase; PIP2: phosphatidylinositol -bisphosphate; PIP3: phosphatidylinositol -trisphosphate; PDK1: phosphoinositide-dependent kinase 1; Raf: rapidly fibrosarcoma; Ras: rat sarcoma; Rheb: Ras homolog enriched in brain; TSC: tuberous sclerosis complex.