Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Mol Diagn Ther. 2017 Dec;21(6):607-620. doi: 10.1007/s40291-017-0289-5.
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.
甲状腺髓样癌（MTC）是甲状腺 C 细胞的增生，占所有甲状腺癌的 5-10%。MTC 可表现为散发性或遗传性形式，已经发现几种分子和信号通路在 MTC 细胞中功能异常。酪氨酸激酶是这些肿瘤细胞中功能异常最受研究的分子。由于其反应有限，化疗药物和放射疗法对治疗晚期转移性 MTC 患者无效。在过去十年中，人们高度关注将多激酶抑制剂作为治疗 MTC 患者的靶向治疗药物，其中酪氨酸激酶抑制剂的研究结果最有希望，这些抑制剂通常与这些激酶的 ATP 结合位点结合。两种药物-凡德他尼和卡博替尼-已被批准用于治疗侵袭性晚期 MTC；然而，这些药物对患者生活质量的毒性和不良反应的潜在影响需要与任何治疗收益进行权衡。根据最近的数据，似乎抑制通路中的一个受体或分子不如同时抑制不同的通路有效，这表明需要使用联合治疗。本综述的主要目的是描述晚期 MTC 治疗中临床特征、分子机制以及目前临床试验中活性的分子和靶向治疗策略。
