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甲状腺癌是目前全球最常见的内分泌系统恶性肿瘤,其中以DTC最常见,主要包括甲状腺乳头状癌(papillary thyroid carcinoma,PTC)和甲状腺滤泡癌(follicular thyroid carcinoma,FTC)2种病理类型。目前,复发风险分层为中高危的DTC患者的标准化治疗方法包括手术、放射性碘(radioactive iodine,RAI)治疗和TSH抑制治疗。对RAI治疗反应评估为疗效不满意的患者往往预后更差。在我国,大部分经标准化治疗的DTC患者5年生存率可达84.3%,然而相较于美国(98.7%)等发达国家[1],生存率的差距仍然值得我们关注。在治疗过程中约23%的DTC患者会发生远处转移,其中约1/3的患者在其自然病程或治疗过程中由于肿瘤细胞丧失摄碘能力,最终发展为放射性碘难治性(radioiodine refractory,RAIR)DTC,其10年生存率仅为10%[2],这部分患者数量的增加可能是目前导致国内外DTC患者生存率差距的原因之一,因此,提高RAIR-DTC患者对RAI治疗的敏感性可能是改善DTC患者预后的关键因素。
众所周知,固有的电离辐射抵抗是大多数癌症患者在放射治疗中面临的主要障碍,不同于外照射,对DTC内照射治疗敏感性的研究一方面在于提高DTC细胞对RAI摄入或减慢DTC细胞对RAI排出的速度,进而增加病灶的有效照射强度;另一方面也应关注在同样有效照射强度下,射线对DTC细胞的杀伤作用,即放射敏感性。
分化型甲状腺癌放射性碘治疗敏感性及其影响因素的研究进展
Research progress on the sensitivity of radioactive iodine therapy and its influencing factors in differentiated thyroid cancer
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摘要: 放射性碘(RAI)治疗是分化型甲状腺癌(DTC)的主要治疗方法之一,其治疗效果主要与肿瘤病灶对RAI 的摄取能力及肿瘤细胞对射线的敏感性有关。对RAI 治疗反应评估为疗效不满意的患者,可以通过上述2个方向来改善其对RAI 治疗的敏感性。笔者通过分析近年来影响DTC患者RAI治疗的相关信号通路及分子机制,总结了影响RAI摄取的包括钠碘同向转运体(NIS)表达及质膜定位的相关机制,以及影响RAI放射敏感性的DNA损伤修复等机制,以期为DTC患者内照射增敏治疗的基础及临床研究提供参考。Abstract: Radioactive iodine (RAI) therapy is one of the critical treatments for differentiated thyroid cancer (DTC). The therapeutic effect is mainly related to the uptake ability of tumor lesions to RAI and radiosensitivity of the tumor cells. The sensitivity to RAI therapy may be improved by the two aforementioned directions in patients who are unsatisfactory in the evaluation of response to RAI therapy. By analyzing the relevant signaling pathways and molecular mechanisms that affect RAI therapy in DTC patients in recent years, the authors summarize the relevant mechanisms affecting RAI uptake, including sodium iodide symporter (NIS) expression and plasma membrane localization, as well as the DNA damage repair mechanisms that affect the radiosensitivity of RAI. It is expected to provide direction for the basic and clinical research of internal irradiation sensitization therapy for DTC patients.
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