在抗HER2治疗后,子宫内膜癌中HER2表达的降低
M Herman Chui1, David N Brown1, Arnaud Da Cruz Paula2
1Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
The Journal of pathology
|November 28, 2023
概括
在HER2阳性子宫内膜癌 (EC) 中,对trastuzumab的耐药性可以通过HER2标表达的丧失而发生. 这通过选择HER2非增强克隆或降低HER2表达的调节来实现,从而影响治疗疗效.
科学领域:
- 在瘤学瘤学.
- 遗传学 遗传学 是一个
背景情况:
- 特拉斯图祖马布对HER2阳性子宫内膜癌 (EC) 有效.
- 获得的抗药性对Trastuzumab是欧洲共同体的一个重大挑战.
- 在EC中抵抗的机制尚不清楚.
研究的目的:
- 为了研究抗HER2治疗后EC瘤的分子变化.
- 为了确定在欧洲共同体中对trastuzumab获得的耐药性机制.
主要方法:
- 使用了目标下一代测序 (NGS),HER2免疫组织化学 (IHC) 和光在位杂交 (FISH).
- 来自14名EC患者的治疗前和治疗后瘤样本的分析,这些患者接受过trastuzumab或trastuzumab emtansine治疗.
- 在一个具有遗传异质性的特定病例上进行了全外体测序.
主要成果:
- 复发性瘤获得了新的遗传改变.
- 在50%的治疗后样本中观察到HER2蛋白表达的降低.
- 失去HER2表达 (4/14名患者) 与保留的HER2基因放大或副本数中性状态有关.
- 在一例具有初级瘤异质性的病例中,HER2非增强克隆的选择发生了.
结论:
- 失去HER2标表达是HER2-阳性EC中抗HER2治疗耐药性的关键机制.
- 机制包括HER2表达的下调和HER2非增强克隆的选择.
- 了解这些机制可以为EC的未来治疗策略提供信息.
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