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The Role of IGF-1R in Pediatric Malignancies

^aPediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA; ^bLombardi Comprehensive Cancer Center, Georgetown University School of Medicine, Washington, DC, USA

Key Words. IGF-1R • Pediatric malignancy • Molecular targeting • Therapeutic antibody

Correspondence: Correspondence: Su Young Kim, M.D., Ph.D., Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, 10 Center Drive, Building 10, CRC 1w-3750, Bethesda, Maryland 20892, USA. Telephone: 301-451-7018; Fax: 301-451-7010; e-mail: kimsuyou{at}mail.nih.gov

Received August 22, 2008; accepted for publication December 1, 2008.

Disclosure: The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the authors, planners, independent peer reviewers, or staff managers.

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.

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