在子宫内膜癌中抑制瘤生长和EMT特征
Philippe A Cassier1, Raul Navaridas2, Melanie Bellina3,4
1Centre Léon Bérard, Departement de Recherche Clinique, Centre de recherche en cancérologie de Lyon INSERM U1052-CNRS UMR5286, Université de Lyon, Université Claude Bernard Lyon1, Centre Léon Bérard, Lyon, France.
Nature
|August 2, 2023
概括
在子宫内膜癌 (EC) 中使用NP137抗体阻断具有前景. 它减少了小鼠和患者的瘤进展,抑制了表皮细胞转化为介质细胞转化 (EMT),并改善了化疗反应.
科学领域:
- 癌症学
- 癌症生物学
- 免疫疗法
背景情况:
- 在癌症中,Netrin-1的调节升高,促进瘤生长.
- 子宫内膜癌 (EC) 呈现出高尼特林-1表达.
- 皮质转化为介质细胞转化 (EMT) 有助于治疗耐药性.
研究的目的:
- 在子宫内膜癌中使用抗网林-1抗体 (NP137) 评估网林-1阻断的疗效.
- 研究NP137的作用机制,包括它对EMT和瘤微环境的影响.
- 在EC小鼠模型中评估NP137与标准化疗的联合治疗.
主要方法:
- 在EC小鼠模型中使用NP137进行Netrin-1阻塞.
- 在晚期EC患者中进行NP137的I期临床试验.
- 瘤基因分析,大量RNA-seq,空间转录组学和单细胞RNA-seq患者活检.
- 在EC小鼠模型中使用NP137与卡博普拉丁- 帕克利塔塞尔的联合治疗.
主要成果:
- 在小鼠模型和人类EC患者中,NP137在减少瘤进展方面表现出有效性 (8/ 14 病情稳定,1 个部分反应).
- NP137抑制了瘤上皮细胞转变为介质细胞 (EMT),诱导了细胞死亡,并改变了免疫透.
- 在EC小鼠模型中,与单独化疗相比,NP137与卡博普拉丁- 帕克利塔塞尔的联合治疗显示出更好的结果.
结论:
- 用NP137阻断内素-1是治疗子宫内膜癌的一个有前途的临床策略.
- 通过诱导脱和抑制EMT,NP137表现出抗瘤作用,可能克服治疗耐药性.
- 这种方法可以提高晚期EC的标准化疗的疗效.
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