Targeting insulin and insulin-like growth factor signalling in oncology.

The family of insulin/insulin-like growth factor (IGF) receptors regulates many crucial aspects of cellular and whole-organism physiology. Evidence that targeting these receptors may be useful in cancer treatment was first recognized more than 20 years ago. Drug development began relatively recently, justified both by laboratory studies and by circumstantial clinical evidence that this receptor family is involved in the molecular pathophysiology of neoplasia. Pharmacologic targeting strategies include both small molecule receptor tyrosine kinase inhibitors and anti-receptor antibodies. More than a dozen drug candidates have been studied preclinically, and several are now being evaluated in clinical trials. These trials have provided evidence suggesting safety of the anti-IGF-I receptor antibodies, a few anecdotes of impressive single-agent activity, and early evidence for a significant improvement in response rate to chemotherapy for lung cancer with co-administration of an anti-IGF-I receptor antibody. This experience has justified expanded clinical trials programs to evaluate several of the IGF-I receptor targeting agents in many different areas of clinical need. Most of these trials will involve assessing activity of rational combinations of IGF-I receptor targeting agents with currently approved drugs.