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Clinical Pharmacology

The Emerging Role of the Insulin-Like Growth Factor Pathway as a Therapeutic Target in Cancer

Massachusetts General Hospital, Boston, Massachusetts, USA

Key Words. Insulin-like growth factor-I • Insulin-like growth factor-II • Insulin-like growth factor-I receptor Breast cancer • Review

Correspondence: Paula D. Ryan, M.D., Ph.D., Massachusetts General Hospital, LRH 308, 55 Fruit Street, Boston, Massachusetts 02114, USA. Telephone: 617-726-5046; Fax: 617-643-0589; e-mail: pdryan{at}partners.org

Disclosure: P.E.G. has acted as a consultant to Novartis, AstraZeneca, and Pfizer, and P.D.R. has acted as a consultant to Pfizer, Genentech, and Novartis. No other potential conflicts of interest were reported by the authors, planners, reviewers, or staff managers of this article.

The insulin-like growth factor signaling pathway is important in many human cancers based on data from experimental models as well as epidemiological studies. Important therapies targeted at this pathway have been or are being developed, including monoclonal antibodies to the insulin-like growth factor-I receptor and small molecule inhibitors of the tyrosine kinase function of this receptor. These investigational therapies are now being studied in clinical trials. Emerging data from phase I trials are encouraging regarding the safety of the monoclonal antibodies. In this manuscript, the rationale for targeting the insulin-like growth factor system is reviewed in addition to a summary of the available clinical trial data.