YAP1定义了一个新兴的,复发小细胞肺癌的塑性人群
C Allison Stewart1, Kavya Ramkumar1, Runsheng Wang1
1Department of Thoracic/Head & Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
bioRxiv : the preprint server for biology
|November 24, 2025
概括
在复发的小细胞肺癌 (SCLC) 中,出现了YAP1阳性细胞,表现出耐药性和大细胞神经内分泌癌 (LCNEC) 的特征. 这些细胞通过改变SCLC表面点来逃避治疗.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 小细胞肺癌 (SCLC) 是一种具有攻击性的神经内分泌瘤,以快速的化学抵抗和不良结果而闻名.
- 在SCLC的转录异质性导致不同的亚型,具有不同的临床脆弱性.
- 在未接受过治疗的SCLC中,YAP1的表达通常不存在.
研究的目的:
- 在标准护理治疗后调查复发性SCLC的特征.
- 为了确定SCLC中与治疗耐药性相关的分子变化.
- 了解YAP1在SCLC治疗失败中的作用.
主要方法:
- 从SCLC患者和临床前模型中分析循环瘤DNA,循环瘤细胞和核心针活检.
- 对YAP1-阳性和YAP1-阴性SCLC细胞进行比较分析.
- 细胞特征的评估,包括衰老,干性和可塑性.
主要成果:
- 在复发性SCLC中出现YAP1阳性细胞群,与治疗耐药性相关.
- 阳性YAP1细胞表现出耐药性持久细胞的特征,包括衰老,干细胞和可塑性.
- 这些细胞从SCLC类进化为大细胞神经内分泌癌 (LCNEC) 类,改变DLL3,SEZ6,B7-H3和TROP2.3等表面标的表达.
结论:
- YAP1的表达与SCLC出现的治疗耐药性有关.
- 阳性YAP1细胞代表了一个强的亚群,可以通过采用LCNEC特征来逃避治疗反应.
- 这种由YAP1驱动的进化突显了SCLC治疗耐药性的机制.
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