Insulin, insulin-like growth factors and neoplasia.

Over the past decade, dozens of epidemiological studies and laboratory experiments have provided evidence for relationships between insulin-like growth factor (IGF) physiology and neoplasia. Population studies provide evidence for a modestly increased risk of a subsequent cancer diagnosis in subjects with IGF-I levels at the high end of the broad normal range, as compared to those at the low end of the normal range. At the cellular level, IGF-I receptor signalling has been shown to play an important role in facilitating the transforming action of a variety of oncogenes. Reducing receptor function with anti-receptor antibodies or specific tyrosine kinase inhibitors reduces the proliferation of many cancers in vitro and in vivo. At present, clinical relevance of the relationship between circulating IGF-I level and cancer risk is limited, but in terms of experimental therapeutics, many clinical trials have been initiated to investigate the possibility that the paradigm of hormonal treatment of cancer may be extended from targeting gonadal steroids to targeting the growth hormone-IGF-I axis.