增加c-SRC表达与肝细胞癌中获得的对lenvatinib的耐药性有关
Masamitsu Takahashi1,2, Takuya Araki1,2, Hideaki Yashima2
1Department of Clinical Pharmacology and Therapeutics, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
Oncology letters
|November 29, 2023
概括
肝细胞癌 (HCC) 中获得的伦瓦提尼布耐药性是一个主要的挑战. 这项研究确定了增加c-SRC表达的关键因素,表明c-SRC抑制是克服HCC中伦瓦替尼抗性的潜在策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 伦瓦提尼布是不可切除的肝细胞癌 (HCC) 的关键治疗方法.
- 对伦瓦提尼布的获得性耐药性导致超过50%的患者在一年内瘤进展.
- 解决伦瓦替尼布耐药性的问题对于改善HCC患者的治疗结果至关重要.
研究的目的:
- 确定导致HCC患者获得伦瓦提尼布耐药性的分子因素.
- 调查特定信号通路和蛋白质在伦瓦提尼布耐药性的作用.
- 探索潜在的治疗策略,针对已识别的抵抗机制.
主要方法:
- 从一个敏感的细胞系 (JHH-7) 建立了一种抗伦瓦替尼布的HCC细胞系 (JHH-7_LR).
- 利用蛋白质组分析来识别耐药细胞中的差异性蛋白质表达.
- 运用发明路径分析 (IPA) 来分析信号路径的变化.
- 研究了使用达沙替尼与伦瓦替尼结合使用c-SRC抑制的效果.
主要成果:
- 蛋白质组分析显示,在1321种检测到的蛋白质中,267种蛋白质的显著表达变化.
- IPA确定了与抵抗相关的多个信号通路中的改变活动.
- 增加c-SRC表达和活性与伦瓦提尼布耐药性有很强的相关性.
- 同时服用达沙替尼布在耐药HCC细胞系中部分恢复了伦瓦替尼布的敏感性.
结论:
- 增加c-SRC表达是HCC获得伦瓦替尼布耐药性的重要因素.
- 抑制c-SRC可能是一个可行的治疗方法来克服伦瓦替尼布耐药性.
- 向c-SRC可能会提高伦瓦替尼治疗肝细胞癌的疗效.
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