对RET阳性非小细胞肺癌治疗药物的膜标的表达
Arianna Marinello1, Maria Rosa Ghigna2, Julia K Rotow3
1Department of Medical Oncology, Gustave Roussy, International Center for Thoracic Cancers, Villejuif, France.
JAMA oncology
|May 29, 2025
概括
患有晚期RET融合阳性非小细胞肺癌 (NSCLC) 的患者通常在RET抑制剂上进展. 这项研究发现MET和TROP2经常表达,这表明这些患者的新治疗点.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 翻译研究是翻译研究.
背景情况:
- 在RET抑制剂 (RETis) 进展后,高级RET融合阳性 (RET+) 非小细胞肺癌 (NSCLC) 患者的选择有限.
- 识别新的膜蛋白点对于开发新疗法至关重要,例如抗体-药物合物和双特异性抗体.
研究的目的:
- 评估RET+ NSCLC中关键膜蛋白标的表达.
- 为了比较RET+NSCLC和RET野生型 (RET-wt) 腺癌之间的标表达.
- 探索与治疗相关的生物标志物联合表达和动态变化.
主要方法:
- 在档案组织上使用集中免疫组织化学 (IHC) 的多中心队列研究.
- 在一个独立的队列上进行全转录组测序 (WTS),用于目标表达分析.
- 使用IHC和WTS对MET,ERBB2,EGFR,HER3和TROP2表达的评估.
主要成果:
- RET+ NSCLC 瘤显示TROP2 (91%) 和MET (59%) 的高表达.
- 与RET-wt对照组相比,RET+NSCLC的MET (59%与43%相比) 显著更高,ERBB2表达率更低 (3.6%与15%).
- 观察到生物标志物的高联合表达 (97%至少有一个阳性) 和配对活检中的动态变化.
结论:
- 与RET-wt瘤相比,RET+NSCLC经常表达MET和TROP2,其中MET富含量较高.
- 同表达和动态生物标志物变化强调了对膜查查的需要.
- 这些发现支持开发针对这些膜蛋白的新型治疗策略,用于高级RET+NSCLC.
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