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Biomarker: IGF-1R (pY)

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IGF-1R (pY)



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Biological or Clinical Significance:

Insulin like growth factor receptor—1 (IGF-1R) is a transmembrane receptor with tyrosine kinase activity found to be over-expressed in many tumor types. The crucial role of IGF-1R receptor signaling in malignant transformation and in tumor cell proliferation and survival makes it a very attractive therapeutic target. Furthermore, in preclinical models, IGF-1R signaling demonstrated to interfere with numerous receptor pathways and was implicated in the mechanism to render tumor cell resistant to chemotherapy, antihormonal therapy and to anti-EGFR and HER2 targeted therapies. Similarly, mammalian target of rapamycin (m-TOR) inhibitors can activate PI3K-Akt pathway via loss of negative feedback on IRS-1 (insulin receptor substrate—1), an effect that can be suppressed by IGF-1R blockade. Binding of IGF-1 or IGF-2 to IGF-1R leads to receptor auto-phosphorylation. Ligand bioavailability is elevated in some tissues and is highly dependent on IGF-binding proteins (IGFBP) and IGFBP-proteases. Activation of the receptor leads to the recruitment of multiple adaptor proteins such as insulin receptor substrates (IRS), Shc and Src homologue and subsequent activation of at least two pro-survival signaling pathways. The main event following IGF-1R phosphorylation is the stimulation of phophoinositol 3-kinase (PI3K)-Akt signaling pathway, leading to cell survival. The second pathway consists of Ras, Raf and extracellular-signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) activation, leading to tumor growth and proliferation.

Ouban A, Muraca P, Yeatman T et al (2003) Expression and Distribution of Insulin-Like Growth Factor-1 Receptor in Human Carcinomas. Hum Pathol 34:803–808

Gualberto A, Pollak M (2009) Emerging role of insulin-like growth factor receptor inhibitors in oncology: early clinicl trial results and future directions. Oncogene 28:1–13

Valentinis B, Baserga R (2001) IGF-I receptor signalling in transformation and differentiation. J Clin Pathol: Mol Pathol 54:133–137

Baserga R, Peruzzi F, Reiss K (2003) The IGF-1 Receptor in Cancer Biology. Int J Cancer 107:873–877

Samani AA, Yakar S, LeRoith D et al (2007) The Role of the IGF System in Cancer Growth and Metastasis: Overview and Recent Insights. Endocr Rev 28:20–47

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