Insulin-like growth factor axis (IGF axis)

The Insulin-like growth factor (IGF) axis is a complex physiological system that plays a central role in regulating growth, development, and metabolism. It consists of two ligands, IGF-1 and IGF-2, which are structurally related to proinsulin; two cell-surface receptors, the IGF-1 receptor (IGF-1R) and the IGF-2 receptor (IGF-2R); and a family of six high-affinity IGF-binding proteins (IGFBP-1 to -6) that modulate ligand bioavailability (Source: PubMed, PMID: 28930943). Signaling is primarily mediated through IGF-1R, a receptor tyrosine kinase that, upon activation, triggers the PI3K/Akt and MAPK pathways to promote cell survival and proliferation (Source: UniProt, P08069). In many human cancers, the IGF axis is over-activated, contributing to tumor growth, metastasis, and resistance to various therapies, making it a significant focus for drug development (Source: NIH, National Cancer Institute). Therapeutic approaches include monoclonal antibodies against IGF-1R or the ligands, as well as small-molecule inhibitors, although their clinical utility has been limited by metabolic side effects like hyperglycemia due to cross-reactivity with the insulin receptor. Additionally, the axis is therapeutically relevant in growth disorders, such as Laron syndrome, using recombinant IGF-1 to bypass growth hormone insensitivity (Source: StatPearls, IGF-1 Deficiency).

Other names

IGF systemSomatomedin axisInsulin-like growth factor signaling pathwayGH/IGF-1 axis

The IGF axis is modulated through several distinct mechanisms: monoclonal antibodies (e.g., teprotumumab, ganitumab) that bind to the extracellular domain of IGF-1R to block ligand binding and induce receptor internalization; small-molecule tyrosine kinase inhibitors (e.g., linsitinib) that inhibit the intracellular signaling of both IGF-1R and the insulin receptor; and ligand-neutralizing antibodies (e.g., xentuzumab) that bind directly to IGF-1 and IGF-2 to prevent receptor activation (Source: PubMed, PMID: 30214318; NIH, National Cancer Institute).