The Insulin-Like Growth Factor (IGF) Signaling Pathway: Strategies for Successful Therapeutic Tasks in Cancer Treatment

The insulin-like growth factor (IGF) system involves a complex network of ligands (IGF-I and IGF-II), receptors (IGF-1R and IGF-2R), IGF-binding proteins (IGFBP-1 to IGFBP-6), and downstream intracellular signaling elements. The IGF-axis modulates proliferation and (anti-)apoptosis in mammals, and it is therefore not surprising that dysregulation of different pathway components is involved in the development and progression of several tumor entities such as breast, prostate, lung, and liver cancer. Because IGFs, IGF-receptors, and IGFBPs play a critical role in the emergence of human neoplasias, these molecules have become the center of special interest as prime targets for potential anti-cancer therapies. In the last decade, various substances and experimental strategies, which affect the IGF-induced signal transduction, have successfully been used in treatment of neoplasias in vitro and in vivo. These approaches contain neutralizing antibodies, antagonistic peptides, selective receptor kinase inhibitors, and (antisense-)oligonucleotides.