Potential Therapeutic Strategies to Interrupt Insulin-Like Growth Factor Signaling in Breast Cancer

Targeting growth factor receptor signaling pathways in breast cancer has proven to be a successful therapeutic strategy. Given the experimental and clinical evidence implicating the involvement of the Insulin-like growth factor (IGF) system in the maintenance of the malignant phenotype of breast cancer, blockade of this receptor system could have clinical implications for the treatment of breast cancer. In theory, there are several ways to disrupt growth factor receptor action. However, the best approach for inhibition of the IGF system has not been clearly defined. Several strategies to disrupt the action of the IGF system have been proposed, including suppression of IGF production, disruption of the ligand-receptor interaction, downregulation of cell surface IGF-IR expression, and inhibition of receptor activation and downstream signaling. These methodologies will be discussed.