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International Journal of Endocrinology
Volume 2013 (2013), Article ID 803171, 16 pages
http://dx.doi.org/10.1155/2013/803171
Review Article

Cellular Signaling Pathway Alterations and Potential Targeted Therapies for Medullary Thyroid Carcinoma

1Department of Pathology, Centro Oncologico Fiorentino, Sesto Fiorentino, 50019 Firenze, Italy
2Department of Internal Medicine, University of Pisa School of Medicine, 56100 Pisa, Italy
3Translational Research Unit, Department of Oncology, Istituto Toscano Tumori, 59100 Prato, Italy

Received 12 November 2012; Revised 8 January 2013; Accepted 10 January 2013

Academic Editor: Eleonore Fröhlich

Copyright © 2013 Serena Giunti et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Parafollicular C-cell-derived medullary thyroid cancer (MTC) comprises 3% to 4% of all thyroid cancers. While cytotoxic treatments have been shown to have limited efficacy, targeted molecular therapies that inhibit rearranged during transfection (RET) and other tyrosine kinase receptors that are mainly involved in angiogenesis have shown great promise in the treatment of metastatic or locally advanced MTC. Multi-tyrosine kinase inhibitors such as vandetanib, which is already approved for the treatment of progressive MTC, and cabozantinib have shown distinct advantages with regard to rates of disease response and control. However, these types of tyrosine kinase inhibitor compounds are able to concurrently block several types of targets, which limits the understanding of RET as a specific target. Moreover, important resistances to tyrosine kinase inhibitors can occur, which limit the long-term efficacy of these treatments. Deregulated cellular signaling pathways and genetic alterations in MTC, particularly the activation of the RAS/mammalian target of rapamycin (mTOR) cascades and RET crosstalk signaling, are now emerging as novel and potentially promising therapeutic treatments for aggressive MTC.