Targeting the insulin-like growth factor axis as a cancer therapy

The insulin-like growth factor (IGF) axis has been implicated in malignant transformation and in tumor cell biology. Human population studies have demonstrated that high levels of circulating IGF-I are associated with an increased risk of certain malignancies. Many model systems show that IGFs stimulate tumor cell proliferation, survival and metastasis. In a new era of anticancer treatments aimed at tumor-specific targets, efforts are in progress for the development of novel anti-IGF therapies. Disrupting type I IGF-receptor (IGF-IR) function in vitro and in vivo results in tumor growth inhibition in several model systems. Antireceptor therapies in particular have provided encouraging results leading to the approval of the first Phase I human clinical trial targeting IGF-IR. Additional methods to decrease levels of circulating IGF-I and II have also been developed. In principle, a benefit of targeted therapies could be their relative lack of toxicity compared with conventional chemotherapy. Anti-IGF-IR therapies, however, raise theoretical concerns for the development of serious side effects, including diabetes. As targeted therapies against the IGF axis continue to be developed, efforts will need to be made to minimize the side effects that result from blocking normal ligand and receptor-induced functions.