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The discovery of the insulin-like growth factor (igf) system occurred half a century ago, in a series of experiments showing that the growth hormone itself exercises no direct metabolic action on skeletal tissues, but rather acts through secondary substances. Those substances were subsequently identified as igf-i and igf-ii. Since then, a series of substances related to igf-i and ii have been found.  So far, the igf system has been determined to consist of 2 ligands (igf-i and -ii), 2 receptors (igf-ir and igfiir), 6 binding proteins (igfbp1–6), and 4 igfbp-related peptides (igfbp Rp1–4). Components of the igf system are found throughout the body in various fluids and tissues 1, and they act on a variety of cells in an endocrine, paracrine, and autocrine manner 2. The igf ligands play a critical role in the growth, development, and maintenance of normal homeostasis, but they have a short lifespan unless attached to a binding protein that transports them in the circulation and delivers them to specific tissues. Binding proteins also regulate igf ligands by modulating their bioavailability to igf receptors. The balance between free igf ligands and igfbp determines the outcome of cells: survival, growth, or apoptosis.

The igf System in Carcinogenesis and Its Implication for Cancer Therapy