在VESPER试验中,基础/状和混合亚型膀癌在新辅助化疗后表现不佳
C S Groeneveld1, C Pfister2, S Culine3
1Institut Curie, PSL Research University, CNRS, UMR144, Equipe Labellisée Ligue Contre le Cancer, Paris; Centre de Recherche des Cordeliers, Université Paris-Cité, UMRS1138, Paris.
概括
肌肉侵入性膀癌 (MIBC) 的基底/状亚型与新辅助化疗 (NAC) 后的较差结果有关. 承认瘤内异质性对于改善治疗策略和患者结果至关重要.
科学领域:
- 在瘤学瘤学.
- 基因组学就是基因组学.
- 癌症生物学 癌症生物学
背景情况:
- 新辅助化疗 (NAC) 是肌肉侵入性膀癌 (MIBC) 的标准,但40%的患者没有反应.
- 生物标志物是需要预测反应或化学抵抗的.
- 基因表达基因亚型,特别是基底亚型在预测NAC反应中的作用尚不清楚.
研究的目的:
- 调查MIBC分子亚型与NAC后的结果之间的关联.
- 探索瘤内部异质性对治疗反应的影响.
- 为了确定预测MIBC中NAC疗效的潜在生物标志物.
主要方法:
- 来自GETUG/AFU VESPER试验的300名接受NAC治疗的MIBC患者的后期分析.
- 病理检查和顺序测定通过尿道的瘤组织.
- 瘤的分类包括基底/状 (Ba/Sq),光线不稳定,丰富的层和混合型,混合型是由瘤内的多个亚型定义的.
- 治疗前和切除囊术后瘤组织的比较 (n=83),以评估免疫变化.
主要成果:
- 与其他亚型相比,基底/状 (Ba/Sq) 亚型 (纯或混合) 与无进展生存的危险比率 (HR 2.0,95% CI 1.36-3.0) 显著增加.
- 混合瘤显示代谢活性下降,可能导致化学抵抗.
- 患有Ba/Sq或混合亚型的非响应者通常在NAC后保持其亚型,并且具有较少的髓状树突细胞.
- 发光性乳头瘤在NAC后显示T CD4+和巨细胞特征增加,而其他亚型没有显著的免疫变化.
结论:
- 在MIBC中,瘤内部的异质性,特别是Ba/Sq亚型,在化学抵抗中起着重要作用.
- 识别这些亚型和异质性对于开发改进的治疗策略至关重要.
- 这些发现提供了洞察力,以增强未来的治疗发展和MIBC患者的结果.
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