Disrupting insulin-like growth factor signaling as a potential cancer therapy.

The type I insulin-like growth factor receptor (IGF-IR) plays multiple roles in several cancers and increased circulating levels of insulin-like growth factor-I (IGF-I) are associated with increased risk of breast, colon, and prostate cancers. Because IGF-II and insulin signal via the insulin receptor (IR) to stimulate the growth of cancer cells, inhibition of IR might be necessary to totally disrupt the action of IGFs and their receptors. This review describes the well-recognized roles of IGF-IR in driving the malignant phenotype, examines the evidence that perhaps IR should also be targeted to inhibit the effects of the IGF ligands and insulin in cancer, describes the strategies to disrupt IGF signaling in cancer, and highlights some key issues that need to be considered as clinical trials targeting IGF-IR proceed.