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Therapeutic Targeting of the IGF Axis
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IGF2/IGF1R Signaling as a Therapeutic Target in MYB-Positive Adenoid Cystic Carcinomas and Other Fusion Gene-Driven Tumors

Sahlgrenska Cancer Center, Department of Pathology, University of Gothenburg, 405 30 Gothenburg, Sweden
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Cells 2019, 8(8), 913; https://doi.org/10.3390/cells8080913
Received: 11 July 2019 / Revised: 13 August 2019 / Accepted: 15 August 2019 / Published: 16 August 2019
Chromosome rearrangements resulting in pathogenetically important gene fusions are a common feature of many cancers. They are often potent oncogenic drivers and have key functions in central cellular processes and pathways and encode transcription factors, transcriptional co-regulators, growth factor receptors, tyrosine kinases, and chromatin modifiers. In addition to being useful diagnostic biomarkers, they are also targets for development of new molecularly targeted therapies. Studies in recent decades have shown that several oncogenic gene fusions interact with the insulin-like growth factor (IGF) signaling pathway. For example, the MYB–NFIB fusion in adenoid cystic carcinoma is regulated by IGF1R through an autocrine loop, and IGF1R is a downstream target of the EWSR1–WT1 and PAX3–FKHR fusions in desmoplastic small round cell tumors and alveolar rhabdomyosarcoma, respectively. Here, we will discuss the mechanisms behind the interactions between oncogenic gene fusions and the IGF signaling pathway. We will also discuss the role of therapeutic inhibition of IGF1R in fusion gene driven malignancies. View Full-Text
Keywords: IGF signaling; IGF2; IGF1R; gene fusions; MYB; adenoid cystic carcinoma; salivary gland tumor; carcinoma; FET oncogenes; sarcoma IGF signaling; IGF2; IGF1R; gene fusions; MYB; adenoid cystic carcinoma; salivary gland tumor; carcinoma; FET oncogenes; sarcoma
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Andersson, M.K.; Åman, P.; Stenman, G. IGF2/IGF1R Signaling as a Therapeutic Target in MYB-Positive Adenoid Cystic Carcinomas and Other Fusion Gene-Driven Tumors. Cells 2019, 8, 913.

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