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Drug Development Series: Review

Disrupting insulin-like growth factor signaling as a potential cancer therapy

Department of Medicine and Cancer Center, University of Minnesota, Minneapolis, Minnesota

Requests for reprints: Deepali Sachdev, University of Minnesota Cancer Center, MMC 806, 420 Delaware Street Southeast, Minneapolis, MN 55455. Phone: 612-626-8487; Fax: 612-626-4842. E-mail: sachd003{at}umn.edu, or Douglas Yee, E-mail: yeexx006{at}umn.edu

Abstract

The type I insulin-like growth factor receptor (IGF-IR) plays multiple roles in several cancers and increased circulating levels of insulin-like growth factor-I (IGF-I) are associated with increased risk of breast, colon, and prostate cancers. Because IGF-II and insulin signal via the insulin receptor (IR) to stimulate the growth of cancer cells, inhibition of IR might be necessary to totally disrupt the action of IGFs and their receptors. This review describes the well-recognized roles of IGF-IR in driving the malignant phenotype, examines the evidence that perhaps IR should also be targeted to inhibit the effects of the IGF ligands and insulin in cancer, describes the strategies to disrupt IGF signaling in cancer, and highlights some key issues that need to be considered as clinical trials targeting IGF-IR proceed. [Mol Cancer Ther 2007;6(1):1–12]

Grant support: NIH grant R01 CA74285 and Public Health Service Cancer Center Support grant P30 CA77398 from the National Cancer Institute (D. Yee).

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ D. Sachdev and D. Yee, unpublished observation.

² http://www.mayoclinic.org/multiple-myeloma/clintrials.html or http://www.moffitt.usf.edu/about_moffitt/publications/clinical_trials_update/nbcmonths/2004s4.pdf.

³ http://www.medical.washington.edu/studies/study_details.asp?study=20051313.

⁴ http://www.clinicaltrials.gov/ct/show/NCT00282737?order=1.

⁵ S. Plymate, personal communication.

⁶ In preparation.

Received 2/13/06; revised 10/ 9/06; accepted 11/20/06.

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