IGF-IR: potential role in antitumor agents

As insulin-like growth factor (IGF) signaling has been recognized to play an important role in human cancer, the IGF-I receptor (IGF-IR) is currently the focus of intensive research aimed at developing novel antitumor agents. The IGF system is frequently deregulated in cancer cells by the establishment of autocrine loops involving IGF-I or -II and/or IGF-IR over-expression. Moreover, epidemiological studies have suggested a link between elevated IGF levels and the development of major human malignancies, such as breast, colon, lung and prostate cancer. Experimental therapies aimed at inhibiting IGF signaling in human tumors involve various approaches, including neutralizing antibodies and pharmacological inhibitors of IGF-IR kinase activity. Although there are numerous reports describing the antitumor activity of such agents against human cancer cell lines propagated in vitro or in experimental animals, it remains unclear how soon the existing drugs will have a demonstrable effect in patients. In this review, we will discuss the evidence implicating the IGF signaling system in the pathology of human cancer and the various strategies that have so far been developed to target the IGF-IR.