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. 2015 Mar 1;2(1):13-25.
doi: 10.1016/j.gendis.2014.10.004.

Insulin-like growth factor (IGF) signaling in tumorigenesis and the development of cancer drug resistance

Sahitya K Denduluri  1 , Olumuyiwa Idowu  1 , Zhongliang Wang  2 , Zhan Liao  3 , Zhengjian Yan  2 , Maryam K Mohammed  1 , Jixing Ye  4 , Qiang Wei  2 , Jing Wang  2 , Lianggong Zhao  5 , Hue H Luu  6
Affiliations

Insulin-like growth factor (IGF) signaling in tumorigenesis and the development of cancer drug resistance

Sahitya K Denduluri et al. Genes Dis. .

Abstract

One of the greatest obstacles to current cancer treatment efforts is the development of drug resistance by tumors. Despite recent advances in diagnostic practices and surgical interventions, many neoplasms demonstrate poor response to adjuvant or neoadjuvant radiation and chemotherapy. As a result, the prognosis for many patients afflicted with these aggressive cancers remains bleak. The insulin-like growth factor (IGF) signaling axis has been shown to play critical role in the development and progression of various tumors. Many basic science and translational studies have shown that IGF pathway modulators can have promising effects when used to treat various malignancies. There also exists a substantial body of recent evidence implicating IGF signaling dysregulation in the dwindling response of tumors to current standard-of-care therapy. By better understanding both the IGF-dependent and -independent mechanisms by which pathway members can influence drug sensitivity, we can eventually aim to use modulators of IGF signaling to augment the effects of current therapy. This review summarizes and synthesizes numerous recent investigations looking at the role of the IGF pathway in drug resistance. We offer a brief overview of IGF signaling and its general role in neoplasia, and then delve into detail about the many types of human cancer that have been shown to have IGF pathway involvement in resistance and/or sensitization to therapy. Ultimately, our hope is that such a compilation of evidence will compel investigators to carry out much needed studies looking at combination treatment with IGF signaling modulators to overcome current therapy resistance.

Keywords: Cancer; Insulin-like growth factor; Resistance; Therapy; Tumorigenesis.

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Figures

Figure 1
Figure 1
Schematic of IGF signaling and major downstream effects. Activation of IGF-1R can result in signaling via two pathways: PI3K/AKT and Ras/MAPK. PI3K/AKT results in decreased apoptosis, increased protein synthesis, and increased glucose metabolism, among various other effects not represented here. Ras/MAPK contains an elaborate kinase cascade that ultimately leads to increased cellular proliferation by promoting the activity of transcription factors, such as ELK1. The activity of IGF ligands is modulated by IGFBPs through direct binding in the extracellular space. IGFBPs also exert several IGF-independent effects via direct interaction with cell membrane-bound proteins, such as integrins.
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References

    1. LeRoith D., Roberts C.T., Jr. The insulin-like growth factor system and cancer. Cancer Lett. 2003;195:127–137. - PubMed
    1. Vincent A.M., Feldman E.L. Control of cell survival by IGF signaling pathways. Growth Horm IGF Res: official journal of the Growth Hormone Research Society and the International IGF Research Society. Aug 2002;12:193–197. - PubMed
    1. Zha J., Lackner M.R. _targeting the insulin-like growth factor receptor-1R pathway for cancer therapy. Clin Cancer Res: an official journal of the American Association for Cancer Research. May 1 2010;16:2512–2517. - PubMed
    1. Siddle K. Signalling by insulin and IGF receptors: supporting acts and new players. J Mol Endocrinol. Aug 2011;47:R1–R10. - PubMed
    1. Kennedy S.G., Wagner A.J., Conzen S.D. The PI 3-kinase/Akt signaling pathway delivers an anti-apoptotic signal. Genes Dev. Mar 15 1997;11:701–713. - PubMed
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