Targeting the IGF1 axis in cancer proliferation

The IGF network of ligands, cell-surface receptors and IGF-binding proteins has important roles at multiple levels, including the cellular, organ and organism levels. The IGF system mediates growth, differentiation and developmental processes, and is also involved in various metabolic activities. Dysregulation of IGF system expression and action is linked to diverse pathologies, ranging from growth deficits to cancer development. Targeting of the IGF axis emerged in recent years as a promising therapeutic approach in conditions in which the IGF system is involved. Specific IGF1 receptor (IGF1R) targeting, in particular, produced the best experimental and clinical results so far, and generated significant optimism in the field. This review provides a basic analysis of the role of the IGF1R in cancer biology and explores the functional interactions between the IGF signaling pathways and various cancer genes (e.g., oncogenes, tumor suppressors). In addition, we review a number of specific malignancies in which the IGF system is involved and summarize recent data on preclinical and clinical studies employing IGF1R-targeted modalities.