在患有DICER1相关瘤的患者中,针对RAS通路的向治疗
Lindy Zhang1, Paige H R Mallinger2,3, Serena Zhou4
1Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
NPJ precision oncology
|July 9, 2025
概括
与DICER1相关的瘤通常具有RAS通路突变. 向疗法显示出潜在的但也具有耐药性机制,在两个儿科病例中观察到BRAF放大和HRAS变异演变.
科学领域:
- 在瘤学瘤学.
- 遗传学 遗传学 是一个
- 分子生物学分子生物学
背景情况:
- 与DICER1相关的瘤经常涉及RAS信号通路突变.
- 针对DICER1瘤中这些合作突变的治疗方法的有效性在很大程度上是未知的.
研究的目的:
- 为了研究分子向药物的疗效,在患有DICER1-关联瘤的儿科患者中,这些瘤含有HRAS或BRAF突变.
- 探索这些瘤中针对向疗法的获得性耐药性的潜在机制.
主要方法:
- 关于两名患有DICER1瘤倾向和DICER1相关瘤的儿童的病例报告.
- 用分子向药物 (达布拉费尼布/特拉美提尼布) 治疗复发/进展的疾病.
- 分子分析以识别突变和跟踪克隆进化,包括BRAF放大和HRAS变异动态.
主要成果:
- 第一个患者在双重dabrafenib/trametinib治疗后出现了BRAF放大,这表明获得了耐药性.
- 在第二名患者中,诊断时存在的亚克隆HRAS变异在尸检中成为主要的克隆,表明其在治疗耐药性方面的作用.
- 这两种病例都显示了可向的HRAS或BRAF突变与DICER1变异合作.
结论:
- RAS/ERK信号传递在DICER1驱动的瘤发生中起着重要作用.
- 针对与DICER1相关的瘤中的合作RAS通路突变是一种潜在的治疗策略.
- 了解抵抗机制,如BRAF放大和HRAS变体的克隆进化,对于优化治疗至关重要.
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