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Updated: Jun 14, 2025

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在ERBB2-放大结肠直肠癌中ctDNA分析:MyPathway试验的生物标志物分析

Funda Meric-Bernstam¹, Kanwal Pratap Singh Raghav², Christopher J Sweeney³

¹Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Clinical cancer research : an official journal of the American Association for Cancer Research

|June 13, 2025

概括

液体活检可以监测HER2阳性结直肠癌治疗反应. 在ctDNA中检测ERBB2放大与结果和抵抗机制相关联.

科学领域:

在瘤学瘤学.
分子诊断学分子诊断
基因组学就是基因组学.

背景情况:

针对HER2的抗体,如珀图祖马布和特拉斯图祖马布 (P+T),在HER2阳性结直肠癌中表现出抗瘤活性.
液体活检是瘤学的新兴工具,但它们在评估ERBB2状态和监测结直肠癌治疗反应方面的有用性尚不清楚.

研究的目的:

为了研究瘤和循环瘤DNA (ctDNA) ERBB2状态之间的一致性.
评估ctDNA用于早期反应监测和识别在HER2-阳性结直肠癌的P + T治疗期间的耐药性机制.

主要方法:

85名ERBB2增强/过度表达的结直肠癌患者接受了P + T.
分析包括在基线和纵向进行ctDNA测试,将ctDNA ERBB2拷贝数与基于组织的下一代测序进行比较.
基因组协同改变和ctDNA动态被评估与治疗反应的关联.

主要成果:

98%的患者在基线时有可检测的ctDNA变异,其中69%显示ERBB2放大.
组织和ctDNA ERBB2复制数之间观察到强烈的相关性.
37%的患者在第3周期,第1天获得了分子反应,这与改善无进展和整体存活率有关.
CDKN2A,KRAS和PIK3CA的突变与较短的整体存活时间有关.
在MAPK,PI3K通路和氨酸受体激酶中出现的共同变化在进展过程中被确定.

结论:

ctDNA可以检测ERBB2放大在大多数患有瘤检测放大的患者.
ctDNA分子反应是改善生存的重要预测因素.
ctDNA协同改变提供了对内在和获得的对HER2向治疗的耐药性机制的见解.

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