The insulin like growth factor-1 receptor (IGF-1R) as a drug target:: novel approaches to cancer therapy

The insulin-like growth factor 1 receptor (IGF-1R) is an important signaling molecule in cancer cells and plays an essential role in the establishment and maintenance of the transformed phenotype. Inhibition of IGF-1R signaling thus appears to be a promising strategy to interfere with the growth and survival of cancer cells. Different classes of molecules, e.g., antisense RNA, monoclonal antibodies and dominant negative IGF-1R gene variants, have been employed towards this aim. These agents have been able to reverse the transformed phenotype in several rodent and human cancer cell lines. The application of peptide aptamers specifically binding to the IGF-1R represents a novel approach to target IGF-1R signaling. The integration of peptide aptamers into targeted protein degradation vehicles and their transduction into cells allows the temporary elimination of the receptor protein. This review summarizes recently published data about inhibition of IGF-1R signaling and provides a perspective on upcoming possibilities. (C) 2004 Elsevier Ltd. All rights reserved.