循环瘤细胞的可塑性通过神经调节素1-HER3信号传递决定了乳腺癌治疗的耐药性
Roberto Würth1,2, Elisa Donato3,4, Laura L Michel5
1Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, Heidelberg, Germany. r.wuerth@dkfz-heidelberg.de.
Nature cancer
|January 3, 2025
概括
我们开发了一种新方法,从乳腺癌患者中培养循环瘤细胞 (CTC). 这种有机体平台揭示了向NRG1-HER3和FGFR1信号通路可以抑制CTC生长和传播.
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:
- 循环瘤细胞 (CTC) 是乳腺癌转移的关键驱动因素,导致患者的治疗结果不佳.
- 由于CTC的数量很少,因此需要先进的方法来研究它们,以了解疾病的进展和治疗疗效.
研究的目的:
- 从转移性乳腺癌患者中建立长期CTC衍生器官.
- 确定控制CTC生存,生长和传播的关键信号通路.
- 探索治疗策略,针对CTC中发现的漏洞.
主要方法:
- 从患者获得的CTC中建立的长期有机体培养.
- 在CTC有机体和临床前异种移植模型上进行了多组学分析.
- 利用全基因组的CRISPR激活屏幕来识别关键的信号通路.
主要成果:
- 确定了神经调节素1 (NRG1) -ERBB2受体氨酸激酶3 (ERBB3/HER3) 信号通路,该通路对于CTC生存和生长至关重要.
- 发现纤维细胞生长因子受体1 (FGFR1) 信号补偿NRG1-HER3轴缺陷.
- 证明了NRG1-HER3和FGFR1信号的联合阻断有效地抑制了CTC的增长.
结论:
- NRG1-HER3和FGFR1信号之间的相互作用是癌细胞可塑性的基础,并提供治疗点.
- 开发的CTC有机体平台是识别患者特定漏洞的宝贵工具.
- 这个平台支持推进转移性乳腺癌的精准医学策略.
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