Classical model of signaling through the IGF-IR. This results in downstream canonical (MAPK)/Ras-Raf-Erk and phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) phosphorylation. IRS, IR substrate; MEK, MAPK kinase; P, phosphorylation. [Adapted from Worrall C, Nedelcu D, Serly J, Suleymanova N, Oprea I, Girnita A, Girnita L. Novel mechanisms of regulation of IGF-1R action: functional and therapeutic implications. Pediatr Endocrinol Rev. 2013;10(4):473–484; © 2019 Illustration Presentation ENDOCRINE SOCIETY].