The Insulin-like Growth Factor System As a Treatment Target in Breast Cancer

Advances in breast cancer treatment have come from the recognition that pathways relevant to cancer cell biology could be identified and targeted. There is abundant in vitro, animal model, and epidemiologic evidence to suggest that the insulin-like growth factors (IGFs) play a role in regulating the malignant phenotype in breast cancer. Insulin-like growth factor action has been implicated in malignant transformation, cellular proliferation, protection from apoptosis, and metastasis. Because IGFs interact with specific cell surface receptors to affect intracellular signaling pathways, blockade of receptor activation could be a successful method to interrupt IGF-driven processes. In contrast to other transmembrane growth factor receptors, the IGF receptor requires activation by ligand. Thus, neutralization of ligand by a "target decoy" could be a useful method to inhibit IGF action. Use of an IGF-binding protein to inhibit activation of IGF receptors will be discussed.