Figure 1.

Targeting the IGF-1R. (A) Working model used to design agents targeting the IGF-1R: linear activation of all downstream signaling pathways triggered by ligand binding to the receptor and intrinsic kinase activation. Briefly: Ligand binding induces auto-phosphorylation of the receptor. This activated confirmation in turn activates two main downstream signaling cascades; mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K), ultimately leading to the biological effects of protein synthesis, cell survival, cell cycle progression, and proliferation. (B) IGF-1R targeting strategies: Two main approaches were taken to inhibit IGF-1R signaling, either by preventing the binding of the ligand to the receptor (IGFBPs, IGF1 peptide analogs or antibodies against the receptor or the ligand) or by blocking the receptor-kinase activation (small molecule tyrosine kinase inhibitors).