Role of Insulin-Like Growth Factor Receptors in Cancer Signaling

  • Douglas YeeEmail author


The insulin-like growth factor signaling system has been implicated in cancer etiology, progression, and metastasis. This signaling system involves a network of highly related ligands and receptors. Targeting of this system is complex; multiple receptors, including the insulin receptor, are involved. Further, holo- and hybrid receptors must be considered when considering therapeutic strategies. This review will evaluate the signaling pathways mediated by this system.


Insulin Insulin-like growth factors Type I insulin-like growth factor receptor Insulin receptor Tyrosine kinase 


  1. 1.
    Pollak MN, Schernhammer ES, Hankinson SE. Insulin-like growth factors and neoplasia. Nat Rev Cancer. 2004;4(7):505–18.CrossRefPubMedGoogle Scholar
  2. 2.
    Leroith D, Kavsan VM, Koval AP, Roberts CT. Phylogeny of the insulin-like growth factors (IGFs) and receptors – a molecular approach. Mol Reprod Dev. 1993;35(4):332–8.CrossRefPubMedGoogle Scholar
  3. 3.
    Guevara-Aguirre J, Balasubramanian P, Guevara-Aguirre M, Wei M, Madia F, Cheng CW, et al. Growth hormone receptor deficiency is associated with a major reduction in pro-aging signaling, cancer, and diabetes in humans. Sci Transl Med. 2011;3(70):70ra13.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Perks CM, Holly JM. IGF binding proteins (IGFBPs) and regulation of breast cancer biology. J Mammary Gland Biol Neoplasia. 2008;13(4):455–69.CrossRefPubMedGoogle Scholar
  5. 5.
    Krywicki RF, Yee D. The insulin-like growth factor family of ligands, receptors, and binding proteins. Breast Cancer Res Treat. 1992;22(1):7–19.CrossRefPubMedGoogle Scholar
  6. 6.
    Yee D. A tale of two receptors: insulin and insulin-like growth factor signaling in cancer. Clin Cancer Res. 2015;21(4):667–9.CrossRefPubMedGoogle Scholar
  7. 7.
    Ekyalongo RC, Yee D. Revisiting the IGF-1R as a breast Cancer target. NPJ Precis Oncol. 2017;1:14.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Baxter RC. IGF binding proteins in cancer: mechanistic and clinical insights. Nat Rev Cancer. 2014;14:329–41.CrossRefPubMedGoogle Scholar
  9. 9.
    White MF. IRS2 integrates insulin/IGF1 signalling with metabolism, neurodegeneration and longevity. Diabetes Obes Metab. 2014;16(Suppl 1):4–15.CrossRefPubMedGoogle Scholar
  10. 10.
    Gradishar WJ, Yardley DA, Layman R, Sparano JA, Chuang E, Northfelt DW, et al. Clinical and translational results of a phase II, randomized trial of an anti-IGF-1R (cixutumumab) in women with breast cancer that progressed on endocrine therapy. Clin Cancer Res. 2016;22(2):301–9.CrossRefPubMedGoogle Scholar
  11. 11.
    Iams WT, Lovly CM. Molecular pathways: clinical applications and future direction of insulin-like growth factor-1 receptor pathway blockade. Clin Cancer Res. 2015;21(19):4270–7.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Becker MA, Ibrahim YH, Oh AS, Fagan DH, Byron SA, Sarver AL, et al. Insulin receptor substrate adaptor proteins mediate prognostic gene expression profiles in breast cancer. PLoS One. 2016;11(3):e0150564.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Tolcher AW, Sarantopoulos J, Patnaik A, Papadopoulos K, Lin CC, Rodon J, et al. Phase I, pharmacokinetic, and pharmacodynamic study of AMG 479, a fully human monoclonal antibody to insulin-like growth factor receptor 1. J Clin Oncol. 2009;27(34):5800–7.CrossRefPubMedGoogle Scholar
  14. 14.
    Macdonald JS, McCoy S, Whitehead RP, Iqbal S, Wade JL 3rd, Giguere JK, et al. A phase II study of farnesyl transferase inhibitor R115777 in pancreatic cancer: a Southwest oncology group (SWOG 9924) study. Investig New Drugs. 2005;23(5):485–7.CrossRefGoogle Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Medicine, Masonic Cancer CenterUniversity of MinnesotaMinneapolisUSA

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