甲状腺癌的“肿瘤时钟”：核心节律网络的致癌机制与治疗机遇

摘要

昼夜节律系统通过CLOCK/BMAL1激活环与PER/CRY抑制环维持24 h生物节律稳态，近年证据提示其失衡与甲状腺癌的发生、去分化、免疫抑制及治疗耐受密切相关。聚焦2019—2025年“甲状腺癌×肿瘤时钟”研究进展，围绕“机制-证据-转化”框架，系统梳理节律网络与MAPK/PI3K/Wnt等致癌信号、缺氧与代谢重编程、DNA损伤修复及免疫微环境耦合的潜在枢纽，并总结节律相关预后模型与人群易感因素。在此基础上，讨论未来应加强时相化采样与动态建模、多中心外部验证及前瞻性时相干预试验，为甲状腺癌分层管理与个体化治疗提供参考。

关键词

甲状腺肿瘤 / 昼夜节律 / CLOCK / BMAL1 / CRY2 / TIMELESS / DNA损伤修复 / 免疫微环境 / 时间治疗学 / 肿瘤生物钟 / 时相治疗

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