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当代肿瘤药物靶点

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Research Article

体外研究表明，IGFR / VEGFR受体串扰和联合抑制在小儿中枢神经系统非典型类畸形横纹肌瘤中的潜力

卷 20, 期 4, 2020

页: [295 - 305] 页: 11

弟呕挨: 10.2174/1568009619666191111153049

价格: $65

摘要

背景：中枢神经系统的非典型类畸胎瘤样横纹肌瘤（CNS ATRT）是一种恶性肿瘤，通常会影响幼儿。导致肿瘤侵袭性和对ATRT中常规疗法耐药的生物学机制尚不清楚。先前的研究表明，胰岛素样生长因子-I受体（IGF-1R）在ATRT肿瘤标本和细胞系中具有活性。在许多癌症类型中，IGF-1R已被证明与其他受体酪氨酸激酶（RTK）发生串扰，从而导致细胞增殖增强。 目的：本研究旨在评估IGF-1受体串扰在ATRT生物学中的作用以及治疗靶向的潜力。 方法：分析源自CNS ATRT标本的细胞系的IGF-1介导的细胞增殖。 IGF-1刺激后进行了全面的受体酪氨酸激酶（RTK）筛选。公开获得的癌症生长抑制数据的生物信息学分析，以鉴定VEGFR抑制剂的IC50与IGF-1R表达之间的相关性。 结果：全面的RTK筛选确定了IGF-1刺激后VEGFR-2的交叉激活。生物信息学分析表明，VEGFR抑制剂阿昔替尼的IC50值与IGF-1R表达呈正相关，支持了IGF-1R在调节抗血管生成疗法反应中的关键作用。 结论：总的来说，我们的数据提供了一种新颖的实验框架，用于评估和利用受体串扰机制来选择有效的药物和组合，以用于ATRT的未来治疗试验。

关键词: 串扰，ATRT，VEGFR，IGF-1R，药物组合，抗血管生成疗法。

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