雌性周期阶段影响乳腺瘤对化疗的敏感性
Laura Bornes1, Lennart J van Winden2, Veerle C M Geurts3
1Division of Molecular Pathology, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
Nature
|December 5, 2024
概括
在雌激素周期内新辅助化疗 (NAC) 的时间会影响乳腺癌治疗反应. 在特异性细胞变化期间启动NAC,导致小鼠和人类的结果较差.
科学领域:
- 生殖生物学
- 癌症学
- 药理学
背景情况:
- 乳腺癌治疗对新辅助化疗 (NAC) 的反应显示出显著的异质性.
- 单独的瘤亚型不能完全解释NAC疗效的差异.
- 生理节奏对癌症治疗的影响仍然是一个活跃的研究领域.
研究的目的:
- 研究乳腺癌对新辅助化疗反应的调节作用.
- 确定化学疗法敏感性循环依赖变化的潜在机制.
- 探索雌激素周期时间对优化NAC结果的临床相关性.
主要方法:
- 利用三种不同的乳腺癌小鼠模型来评估基于治疗开始时间的NAC反应 (期与二期).
- 分析了绝经前人类患者队列的回顾性数据,以将雌激素周期阶段与NAC结果相关联.
- 研究的机理因素包括表皮转移到介质细胞 (EMT),瘤血管和免疫细胞透 (巨细胞) 在不同周期阶段.
主要成果:
- 在小鼠模型中,在期开始使用NAC的疗效与期开始使用NAC相比有所降低.
- 对人类的回顾性数据证实了这些发现,表明更年期前患者的情况类似.
- 迪奥斯特与EMT增加,瘤血管直径减少和巨细胞存在的增加有关,所有这些都与化疗抵抗有关.
结论:
- 雌激循环是影响乳腺癌化学敏感性的重要红外线节奏.
- 期呈现生物条件,降低新辅助化疗的有效性.
- 针对依赖雌激素周期的因素,如巨细胞透,以及优化治疗时间,有可能改善NAC的结果.
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