在具有可变HER2表达的小儿固体瘤中,特鲁苏马布德鲁克斯坦的抗瘤活性
Chelsey M Burke1, Tamar Y Feinberg1, Samantha Brosius2
1Memorial Sloan Kettering Cancer Center, New York, NY, United States.
Molecular cancer therapeutics
|September 5, 2025
概括
在儿童癌症中,超出HER2表达的特拉斯图祖马布德鲁克斯坦 (T-DXd) 具有活性. 骨肉瘤是耐药的,而DSRCT和瘤受益于T-DXd,这表明生物标志物无关的发展.
科学领域:
- 癌症学
- 药理学
- 翻译医学
背景情况:
- 特拉斯图苏巴德鲁克斯坦 (T-DXd) 是一种针对HER2的抗体药物联合体 (ADC),有效治疗成人癌症.
- 之前的研究表明HER2在骨肉瘤 (OS) 中表达,导致在儿童OS患者中进行临床试验,该试验被提前终止.
- 在具有可变HER2表达的儿科癌症中,T-DXd的疗效需要进一步研究.
研究的目的:
- 在儿童癌症模型中评估T-DXd的活性,包括骨肉瘤 (OS).
- 评估HER2表达在各种儿童瘤类型的T-DXd疗效中的作用.
- 探索T-DXd活动的潜在非HER2介导机制,并确定新的治疗机会.
主要方法:
- 在骨髓瘤患者衍生的异种移植 (PDX) 模型中测试T-DXd活性.
- 在31个儿童癌细胞系中评估T-DXd的疗效.
- 在儿科瘤和小圆细胞瘤的PDX模型中评估T-DXd活性 (DSRCT).
主要成果:
- 尽管无法检测HER2表达,但T-DXd在OS PDX模型中显示了22%的客观反应率.
- 骨髓瘤细胞系对T-DXd和未结合的德鲁克斯坦有抗性.
- 在儿童瘤和DSRCT中,T-DXd显示了HER2增强和非HER2介导的活性,具有对照ADC的同效.
结论:
- 在儿童癌症中,HER2不是T-DXd反应的可靠生物标志物.
- T-DXd表现出显著的非HER2介导活性,特别是在对有效载荷敏感的瘤组织结构中.
- 在DSRCT和儿科瘤中,T-DXd的生物标志性临床发展是有必要的.
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