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]
- insulin-like growth factors
- insulin
- type I IGF receptor
- insulin receptor
- targeted therapy; antibodies
Footnotes
↵1 D. Sachdev and D. Yee, unpublished observation.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.
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.
- Accepted November 20, 2006.
- Received February 13, 2006.
- Revision received October 9, 2006.
- American Association for Cancer Research
Volume 6, Issue 1
