在细胞对瘤治疗场 (TTFields) 的反应中,PI3K/AKT信号通路的作用
Anat Klein-Goldberg1, Tali Voloshin2, Efrat Zemer Tov1
1Novocure Ltd, Haifa, Israel.
Cell death & disease
|March 28, 2025
概括
通过抑制PI3K/AKT通路,可以提高瘤治疗场 (TTFields) 疗效. 这条由TTFields激活的途径促进了癌细胞的存活,但其抑制使瘤对TTFields治疗敏感.
科学领域:
- 在瘤学瘤学.
- 癌症生物学 癌症生物学
- 生物化学 生化学
背景情况:
- 瘤治疗场 (TTFields) 是一种成熟的癌症治疗方法.
- 基因组研究表明,PIK3CA突变可能会对TTFields产生抗性.
- 在TTFields响应中PI3K/AKT途径的作用尚未完全理解.
研究的目的:
- 研究PI3K/AKT途径在TTFields响应中的作用.
- 为了确定由TTFields激活PI3K/AKT的机制.
- 评估结合的TTFields和PI3K抑制作为治疗策略.
主要方法:
- 在质母细胞瘤,卵巢和肺癌细胞系中利用了Luminex多重测定和西部抹杀.
- 在小鼠中使用 ортотоп瘤模型进行了体内验证.
- 使用PI3K抑制剂与TTFields结合进行的抑制试验.
主要成果:
- TTFields处理导致AKT信号的时间依赖激活.
- 焦点粘附激酶 (FAK) 和N-cadherin介导AKT酸化和细胞存活.
- 药理上抑制PI3K使癌细胞在体外和体内对TTFields敏感.
结论:
- PI3K/AKT通路是癌细胞对TTFields反应的关键媒介.
- AKT激活受细胞表面和细胞间相互作用的影响.
- 抑制PI3K/AKT通路是一个有前途的策略,可以提高TTFields的疗效.
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