The
insulin-like growth factor (IGF) signaling system plays a crucial role in human
cancer and the
IGF-1 receptor (IGF-1R) is an attractive
drug target against which a variety of novel anti-
tumor agents are being developed. Deregulation of the IGF signaling pathway frequently occurs in human
cancer and involves the establishment of autocrine loops comprising
IGF-1 or
IGF-2 and/or IGF-1R over-expression. Epidemiologic studies have documented a link between elevated IGF levels and the development of solid
tumors, such as breast, colon, and
prostate cancer. Anti-
cancer strategies targeting the IGF signaling system involve two main approaches, namely
neutralizing antibodies and small molecule inhibitors of the IGF-1R
kinase activity. There are numerous reports describing anti-
tumor activity of these agents in pre-clinical models of major human
cancers. In addition, multiple clinical trials have started to evaluate the safety and efficacy of selected IGF-1R inhibitors, in combination with standard chemotherapeutic regimens or other targeted agents in
cancer patients. In this mini review, I will discuss the role of the IGF signaling system in human
cancer and the main strategies which have been so far evaluated to target the IGF-1R.