The IGF-1 receptor and its contributions to metastatic tumor growth-novel approaches to the inhibition of IGF-1R function.

Signals originating from the type 1 insulin-like growth factor receptor (IGF-1R) have pleiotropic effects on cell behavior. They regulate cell proliferation, survival, differentiation and transformation. IGF-1R also plays an essential role in the multistep process of cancer cell metastasis. Metastatic spread of tumor cells is the main reason for the high mortality rates associated with cancer. The development of strategies to inhibit this process promises important clinical benefits. Current attempts to block IGF-1R signaling has resulted in the reversion of the transformed phenotype, the induction of apoptosis, the sensitization to chemotherapeutic drugs and the reduction of the metastatic propensity of tumor cells. Since inhibition of IGF-1R has acceptable side effects on normal cells, the IGF-1R represents a favorable target for anticancer therapy. The well known structure and biochemical functions of the receptor suggest diverse strategies for interference. We will discuss strategies which have already been developed and suggest novel approaches based on peptide aptamers. These are peptides selected for specific binding to defined domains of the IGF-1R which offer subtle and specific possibilities to interfere with IGF-1R in the context of experimental tumor therapy.