Insulin-like growth factor pathway (IGF pathway)

The insulin-like growth factor pathway is a hormone-regulated signal transduction network critical for cell growth, survival, and metabolism in both physiological and pathological contexts. This pathway involves two main peptide ligands (IGF-1 and IGF-2), their receptors (insulin-like growth factor 1 receptor [IGF-1R], insulin-like growth factor 2 receptor [IGF-2R], and insulin receptor), and high-affinity binding proteins (IGFBP1-6) that modulate ligand bioavailability. Activation of IGF-1R by IGF-1 or IGF-2 triggers downstream signaling cascades including PI3K/Akt and Ras/MAPK, promoting proliferation and inhibiting apoptosis. The pathway is tightly linked to human cancers, metabolic disorders, and growth abnormalities. Therapeutic targeting has focused primarily on antagonism of IGF-1R with monoclonal antibodies or small-molecule inhibitors, but clinical challenges such as metabolic toxicity and resistance mechanisms have limited success to date[1][2][5][8]. Note: - The "Insulin-like growth factor pathway" is not a single molecular entity but rather encompasses a family of ligands, binding proteins, and receptors. For structured molecular target data, it is recommended to use explicit canonical names such as "Insulin-like growth factor 1 receptor (IGF-1R)" for the receptor, "Insulin-like growth factor 1 (IGF-1)" for the ligand, etc.[1][2][4][7].

Other names

IGF axisIGF signalling pathwayIGF systemInsulin-like growth factor signaling axis

Inhibition of ligand binding (by blocking IGF-1/IGF-2 to receptor) Blockade of receptor tyrosine kinase activity Antagonism of signal transduction (e.g., blocking PI3K/Akt, MAPK pathways) Induction of receptor internalization/degradation