Anti-insulin-like growth factor strategies in breast cancer.

The insulin-like growth factors (IGF-I and -II) are potent mitogens and survival factors for both normal and malignant breast cells. These effects are mediated primarily through the IGF-I receptor (IGF-IR), which is significantly overexpressed and highly activated in breast tumors. The IGF-binding proteins are competitive inhibitors of IGF/IGF-IR interaction, limiting cellular proliferation and survival. Higher serum IGF-I levels or an increased ratio of IGF-I to IGF binding protein-3 is associated with an increased risk of developing breast cancer. Hence, interest in the IGF system as a potential target for the development of novel antineoplastic therapies has ensued. Several strategies to interrupt IGF-IR signaling are currently being evaluated for the treatment of breast cancer, including suppression of IGF production, reduction of functional IGF-IR levels, neutralization of IGF action, and inhibition of IGF-IR activation.