未分化及失分化甲状腺癌治疗进展

Progress in the Treatment of Anaplastic and Dedifferentiated Thyroid Cancer

未分化及失分化甲状腺癌是死亡率较高的内分泌恶性肿瘤,目前尚缺乏有效的治疗手段,寻找新的治疗手段显得尤为迫切。一系列新的治疗方法的出现为未分化及失分化甲状腺癌患者的治疗提供了可能:基因治疗,如通过恢复抑癌基因功能的基因治疗(恢复P53基因功能)或自杀基因导入治疗,抗肿瘤血管形成的基因治疗,钠/碘转运蛋白(NIS)基因介导的放射性碘治疗;诱导分化治疗如:通过维甲酸及组蛋白乙酰化酶抑制剂诱导分化治疗可促进肿瘤细胞的分化,有助于控制肿瘤的发展,而金属蛋白酶抑制剂的应用可控制肿瘤细胞的转移。而手术方式、放化疗方案的改进及综合应用亦可延长甲状腺未分化及失分化癌患者的生存时间。本文就上述新的甲状腺癌的治疗方案做一综述。

Anaplastic and dedifferentiated thyroid carcinomas are typically lethal malignancies that occur in the endocrine system that currently do not have any effective therapy. Development and evaluation of novel treatment strategies for these types of carcinoma are urgently needed. A variety of new therapies for anaplastic and dedifferentiated thyroid cancer has been evaluated, including corrective gene therapy （p53 restoration）, cytoreductive gene therapy （suicide gene/prodrug strategy herpes simplex virus-thymidine kinase [HSV-tk]/ganciclovir）, antiangiogenic gene therapy, and immunomodulatory gene therapy （expression of interleukin （IL）-2 and IL-12）. Cloning of the sodium iodide symporter （NIS） gene has paved the way for the development of a novel cytoreductive gene therapy strategy based on NIS gene transfer followed by the application of radioactive iodine therapy （1311）. Histone acetylation inhibitors and retinoic acid-induced differentiation therapy can inhibit tumor progression. Metalloproteinase inhibitor therapy can inhibit the metastasis of tumors. A combination of different therapies, including surgical resection, chemotherapy and radiotherapy, has been shown to be helpful in enhancing therapeutic efficacy. This article reviews recent progress in the treatment of anaplastic and dedifferentiated thyroid cancer.