Division of Head and Neck Medical Oncology, Istituto Nazionale Tumori di Napoli "Fondazione G. Pascale-IRCCS", Naples, Italy.
Division of Thyroid and Parathyroid Surgery, Istituto Nazionale Tumori di Napoli "Fondazione G. Pascale-IRCCS", Naples, Italy.
Crit Rev Oncol Hematol. 2015 Apr;94(1):55-63. doi: 10.1016/j.critrevonc.2014.10.012. Epub 2014 Nov 1.
Thyroid carcinomas are rare and heterogeneous diseases representing less than 1% of all malignancies. The majority of thyroid carcinomas are differentiated entities (papillary and folliculary carcinomas) and are characterized by good prognosis and good response to surgery and radioiodine therapy. Nevertheless, about 10% of differentiated carcinomas recur and become resistant to all therapies. Anaplastic and medullary cancers are rare subtypes of thyroid cancer not suitable for radioiodine therapy. A small percentage of differentiated and all the anaplastic and medullary thyroid carcinomas often recur after primary treatments and are no longer suitable for other therapies. In the last years, several advances have been made in the field of molecular biology and tumorigenesis mechanisms of thyroid carcinomas. Starting from these issues, the targeted therapy may be employed as a new option. The MAP-Kinase pathway has been found often dysregulated in thyroid carcinomas and several upstream signals have been recognized as responsible for this feature. RET/PTC mutations are often discovered both in papillary and in medullary carcinomas, while B-RAF mutation is typical of papillary and anaplastic histologies. Also mTOR disruptions and VEGFR pathway disruption are common features in all advanced thyroid cancers. Some angiogenesis inhibitors and a number of RET/PTC pathway blocking agents are yet present in the clinical armamentarium. Vandetanib, cabozatinib and sorafenib have reached clinical use. A number of other biological compounds have been tested in phase II and III trials. Understanding the biology of thyroid cancers may help us to design a well shaped targeted therapy.
甲状腺癌是一种罕见且异质性的疾病，占所有恶性肿瘤的比例不到 1%。大多数甲状腺癌是分化型实体（乳头状和滤泡状癌），其特点是预后良好，对手术和放射性碘治疗反应良好。然而，约 10%的分化型癌会复发并对所有治疗产生耐药性。间变性和髓样癌是不适合放射性碘治疗的甲状腺癌罕见亚型。一小部分分化型和所有间变性和髓样甲状腺癌在初次治疗后经常复发，不再适合其他治疗。近年来，在甲状腺癌的分子生物学和肿瘤发生机制领域取得了多项进展。从这些问题出发，靶向治疗可能成为一种新的选择。MAP-Kinase 通路在甲状腺癌中经常失调，已经发现了几个上游信号负责这种特征。RET/PTC 突变通常在乳头状癌和髓样癌中发现，而 B-RAF 突变是乳头状癌和间变性组织学的典型特征。此外，mTOR 中断和 VEGFR 通路中断也是所有晚期甲状腺癌的常见特征。一些血管生成抑制剂和一些 RET/PTC 通路阻断剂已在临床上应用。凡德他尼、卡博替尼和索拉非尼已被应用于临床。还有许多其他生物化合物已在 II 期和 III 期试验中进行了测试。了解甲状腺癌的生物学特性可能有助于我们设计出针对性更强的治疗方案。
