IGF system in cancer: from bench to clinic

Insulin-like growth factors (IGFs) are important mediators of growth, development, and survival, and have been implicated in the pathogenesis of malignancies. The IGF system is a complex system comprising two growth factors (IGF-I and IGF-II), cell surface receptors (IGF-IR and IGF-IIR), six specific high-affinity binding proteins (IGFBP-1 to IGFBP-6), IGFBP proteases, and several other IGFBP-interacting molecules that regulate and propagate IGF actions in several tissues. IGFs are produced by almost any cell in the body; circulate in more than 1000-fold higher concentrations than most other peptide hormones, such as insulin, and their action is modulated by several binding proteins. Studies have revealed that IGFs may promote cell cycle progression and inhibition of apoptosis either by directly associating with other growth factors or indirectly by interacting with other molecular systems that have an established role in carcinogenesis and cancer promotion, such as steroid hormones and integrins. In addition, studies also suggest that increased serum levels of IGFs and/or altered levels of their binding proteins are associated with increased risk of developing cancers. These data underline the significance of IGFs system in the development of cancer risk, and a potential target for novel anticancer treatments and/or preventative strategies in high-risk groups. The researchers review the IGFs pathway and its implications in cancer development and treatment.