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在细胞瘤患者中抑制MEK的有效性
Eli L Diamond1,2, Benjamin H Durham3,4, Gary A Ulaner2,5
1Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Nature
|March 15, 2019
概括
基质细胞瘤依赖于MAPK信号传递. 在患有BRAF突变和没有BRAF突变的患者中,科比美替尼 (一种MEK抑制剂) 的试验显示出高响应率,为所有类型的细胞瘤提供了新的治疗方法.
科学领域:
- 癌症学
- 血液学
- 分子生物学
背景情况:
- 囊性瘤是多种类型的克隆性造血性疾病.
- 基因激活蛋白激酶 (MAPK) 途径的突变很常见.
- 针对BRAF V600突变存在向治疗,但其他突变没有.
研究的目的:
- 调查细胞瘤中的ERK依赖性.
- 评估瘤基因型不论如何,可比米替尼 (一种MEK抑制剂) 的疗效.
- 在接受治疗的患者中描述MAPK路径的变化.
主要方法:
- 使用科比米提尼布的概念验证临床试验.
- 不论瘤的基因型如何,都需要注册患有囊细胞瘤的患者.
- 对ERK激活能力的MAPK变化的并行表征.
主要成果:
- 在18名接受治疗的患者中观察到89%的总体反应率.
- 反应是持久的,在一年内100%的持续和94%的无进展生存率.
- 在各种MAPK路径突变 (ARAF,BRAF,RAF1,NRAS,KRAS,MEK1,MEK2) 中,科比美替尼有效.
结论:
- 囊瘤对MAPK信号产生显著依赖.
- 用科比美尼布抑制MEK是一种有效的治疗策略,适用于全方位的瘤.
- 这项研究将分子向治疗的好处扩展到所有患有细胞瘤的患者.
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