Insulin-like growth factor-I and the gastrointestinal system: Therapeutic indications and safety implications

Abstract

Following the identification of insulin-like growth factor-I (IGF-I) as a potent trophic factor for the intestine over a decade ago, therapeutic indications have been identified for a range of candidate bowel disorders and diseases in which accelerated intestinal repair is desirable. Subsequent experimental studies in experimentally-induced animal models and genetically-modified mice have supported a therapeutic role for IGF-I in facilitated repair processes in gastrointestinal disorders including radiation enteritis, chemotherapy-induced mucositis and inflammatory bowel disease, conditions associated with either the pre-existence of malignancy or a predisposition to develop neoplasia. Moreover, recent evidence from in vitro, in vivo and human population studies is suggestive of an active role for IGF-I in the development and progression of certain cancers, and although causality remains unproven, antagonism of IGF-I action is being pursued as a potential chemo-preventive strategy. Novel milk and colostrum-derived bioactive formulations containing IGF-I are being developed as adjunctive treatment modalities for certain bowel disorders. Understanding the precise role of the IGF axis in cancer will either identify antagonism of the IGF-I/receptor interaction as an important approach in cancer prevention and risk reduction, or alternatively, support further development of IGF-I as a promising treatment modality for acute gastrointestinal disease.