The Role of IGF-1R in Pediatric Malignancies

The insulin-like growth factor (IGF) family consists of ligands (IGF-I, IGF-II, insulin), several receptors (including IGF-1R), and six binding proteins (IGFBP-1 through IGFBP-6). Members of this family regulate key cellular activities and they also play an important role in the development and progression of both adult and childhood cancers. Binding of a ligand to the receptor leads to its activation, followed by signal transduction along several pathways. In some childhood malignancies, IGF-1R can be activated by endocrine, autocrine, or paracrine mechanisms. Although mutations in IGF-1R have not been identified, this signaling pathway is upregulated in many childhood cancers. These findings have led to the development of a host of IGF-1R signaling modulators that are currently being tested in clinical trials. This review explores the role of IGF-1R in a range of childhood malignancies. The Oncologist 2009; 14: 83-91