Introduction of Insulin-like growth factors (IGFs)

The insulin-like growth factors (IGFs) were first identified over 50 years ago and it has been over 30 years since their receptors were discovered and characterized. Radiolabeling experiments eventually helped to identify the receptor for IGF1, and the first report of a role for IGF1R in human cancers was by Pollak et al. in 1987 who used competitive binding assays to identify specific docking sites for IGF1 in breast and colon tumor biopsy specimens.The IGF signaling system family itself is composed of the three ligands IGF-1, IGF-2, and insulin; three cell membrane receptors–type 1 and 2 IGF receptors (IGF-1R and IGF-2R) and the insulin receptor (IR); seven high-affinity binding proteins (IGFBP 1-7); and several associated proteins, namely IRS and shc. These lead to two main signaling cascades: the PI3K/Akt and Ras/Raf/MEK/ERK pathways, which ultimately result in suppressed apoptosis, cell proliferation and invasion, and enhanced cell survival. Other studies are beginning to uncover the important role the IGFs play in diseases such as cancer and diabetes, showing for instance that IGF-1 stimulates growth of both prostate and breast cancer cells. Researchers are not in complete agreement about the degree of cancer risk that IGF-1 poses.