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Activation of the IGF Axis in Thyroid Cancer: Implications for Tumorigenesis and Treatment

1
Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy
2
Center of Experimental Oncology and Hematology, A.O.U. Policlinico-Vittorio Emanuele, 95123 Catania, Italy
3
Department of Medical Oncology A.O.U. Policlinico-Vittorio Emanuele, 95123 Catania, Italy
4
Endocrinology, Department of Clinical and Experimental Medicine, Garibaldi-Nesima Medical Center, University of Catania, 95122, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(13), 3258; https://doi.org/10.3390/ijms20133258
Received: 13 June 2019 / Revised: 28 June 2019 / Accepted: 28 June 2019 / Published: 2 July 2019
(This article belongs to the Special Issue Cell and Molecular Biology of Thyroid Disorders 2.0)
The Insulin-like growth factor (IGF) axis is one of the best-established drivers of thyroid transformation, as thyroid cancer cells overexpress both IGF ligands and their receptors. Thyroid neoplasms encompass distinct clinical and biological entities as differentiated thyroid carcinomas (DTC)—comprising papillary (PTC) and follicular (FTC) tumors—respond to radioiodine therapy, while undifferentiated tumors—including poorly-differentiated (PDTC) or anaplastic thyroid carcinomas (ATCs)—are refractory to radioactive iodine and exhibit limited responses to chemotherapy. Thus, safe and effective treatments for the latter aggressive thyroid tumors are urgently needed. Despite a strong preclinical rationale for targeting the IGF axis in thyroid cancer, the results of the available clinical studies have been disappointing, possibly because of the crosstalk between IGF signaling and other pathways that may result in resistance to targeted agents aimed against individual components of these complex signaling networks. Based on these observations, the combinations between IGF-signaling inhibitors and other anti-tumor drugs, such as DNA damaging agents or kinase inhibitors, may represent a promising therapeutic strategy for undifferentiated thyroid carcinomas. In this review, we discuss the role of the IGF axis in thyroid tumorigenesis and also provide an update on the current knowledge of IGF-targeted combination therapies for thyroid cancer. View Full-Text
Keywords: IGF axis; thyroid cancer; therapeutic approach IGF axis; thyroid cancer; therapeutic approach
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Manzella, L.; Massimino, M.; Stella, S.; Tirrò, E.; Pennisi, M.S.; Martorana, F.; Motta, G.; Vitale, S.R.; Puma, A.; Romano, C.; Di Gregorio, S.; Russo, M.; Malandrino, P.; Vigneri, P. Activation of the IGF Axis in Thyroid Cancer: Implications for Tumorigenesis and Treatment. Int. J. Mol. Sci. 2019, 20, 3258.

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