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Medullary Thyroid Cancer: Clinical Characteristics and New Insights into Therapeutic Strategies Targeting Tyrosine Kinases

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Abstract

Medullary thyroid carcinoma (MTC) is a hyperplasia of thyroid C-cells, accounting for 5–10% of all thyroid cancers. MTCs may appear as sporadic or hereditary forms, and several molecules and signaling pathways have been found to function defectively in MTC cells. Tyrosine kinases are the most well-studied molecules that have abnormal function in these tumor cells. Due to their limited response, chemotherapeutic agents and radiation therapy are not effective in treating patients with advanced metastatic MTC. In the past decade, significant attention has been given to the utilization of multikinase inhibitors as targeted therapeutic agents for treating MTC patients, with the most promising results arising from the study of tyrosine kinase inhibitors, which generally bind to the ATP binding sites of these kinases. Two drugs—vandetanib and cabozantinib—are approved for the treatment of aggressive advanced MTC; however, the potential for toxicities and adverse effects of these agents on patient quality of life need to be considered against any therapeutic gain. According to recent data, it appears that inhibition of only one receptor or molecule in a pathway is not as effective as simultaneous inhibition of different pathways, indicating the need to use combination therapy. The main purpose of this review is to describe the clinical characteristics, molecular mechanisms, and current molecular and targeted therapeutic strategies active in clinical trials for advanced MTC treatment.

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Acknowledgements

The authors are grateful to Dr. Javad Sharifi-Rad, Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran, for critically reading the manuscript.

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  1. Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Sadegh Rajabi

  2. Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Mehdi Hedayati

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  1. Sadegh Rajabi
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Rajabi, S., Hedayati, M. Medullary Thyroid Cancer: Clinical Characteristics and New Insights into Therapeutic Strategies Targeting Tyrosine Kinases. Mol Diagn Ther 21, 607–620 (2017). https://doi.org/10.1007/s40291-017-0289-5

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