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DTC占所有甲状腺癌的90%以上[1],部分DTC患者可在自然状态下或治疗过程中失分化而发展为放射性碘难治性DTC(radioiodine refractory DTC,RAIR-DTC),其10年生存率低于10%[2]。有研究者发现,RAIR-DTC的发生、发展与许多基因密切相关[3]。由于RAIR-DTC细胞摄碘量减少甚至不摄碘,导致131I治疗疗效差。因此主要借助分子靶向药物结合TSH进行抑制治疗,如抗血管生成多激酶抑制剂,通过抑制血管内皮生长因子和其同源血管内皮生长因子受体之间的相互作用,从而干扰肿瘤形成、生长和转移所需的血管生成。然而,分子靶向药物往往会给患者带来明显的全身不良反应,且医师对患者的选择及适应证的把握存在困难,也会影响患者对药物使用的依从性;另外,分子靶向药物价格昂贵,会加重患者经济负担。因此,明确DTC细胞发生失分化的分子机制,应用分子靶向药物抑制相关基因,诱导DTC细胞再分化,恢复RAIR-DTC细胞的摄碘能力,再结合131I治疗的治疗方案应运而生。
放射性碘难治性分化型甲状腺癌去分化分子机制及再分化治疗的分子靶向药物
Molecular mechanism of dedifferentiation and molecular targeted drugs for redifferentiation therapy of radioiodine refractory differentiated thyroid cancer
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摘要: 甲状腺癌是最常见的内分泌肿瘤,其中分化型甲状腺癌(DTC)占90%以上。DTC患者预后良好,但仍有局部复发和远处转移的风险。多数DTC患者的肿瘤细胞基底膜中钠/碘同向转运体表达障碍,导致肿瘤细胞摄碘能力降低,最终进展为放射性碘难治性DTC(RAIR-DTC),此类患者预后较差。笔者就DTC失分化的相关基因及当前文献报道的可逆转RAIR-DTC细胞摄碘能力的分子靶向药物进行综述。Abstract: Thyroid cancer is the most common endocrine tumor, of which differentiated thyroid cancer (DTC) accounts for more than 90%. The prognosis of patients with DTC is good, but there is still a risk of local recurrence and distant metastasis. The expression of sodium/iodine symporter in the basement membrane of tumor cells in most DTC patients is impaired, which led to the iodine uptake capacity of tumor cell is decreased, and the final progression is radioiodine refractory DTC (RAIR-DTC). The prognosis of these patients is poor. This paper reviews the genes related to DTC dedifferentiation and the molecular targeted drugs that can reverse RAIR-DTC cell iodine uptake reported in the literature.
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Key words:
- Thyroid neoplasms /
- Iodine radioisotopes /
- Cell dedifferentiation /
- Molecular targeted therapy /
- Genes
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