在肝细胞癌中,EGFR旁路激活介导获得的对regorafenib的耐药性
Lili Hu1,2, Weiwei Shi1,3, Kua Liu4
1Division of Hepatobiliary and Transplantation Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
通过激活旁路通路,EGFR过度表达驱动肝癌中对regorafenib的耐药性. 用gefitinib准表皮生长因子受体 (EGFR) 使瘤对regorafenib重新敏感,为晚期肝细胞癌 (HCC) 提供了潜在的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 药物耐药性 药物耐药性 药物耐药性
背景情况:
- 雷戈拉菲尼布是一种氨酸激酶抑制剂 (TKI),用于治疗不可切除的肝细胞癌 (HCC).
- 获得的耐药性限制了regorafenib的疗效,而绕道激活是关键机制.
- 有限的研究存在于特定于HCC.regorafenib耐药性的旁路激活.
研究的目的:
- 调查绕道激活机制,有助于HCC.regorafenib耐药性.
- 评估准表皮生长因子受体 (EGFR) 克服这种抗性的潜力.
主要方法:
- 高通量蛋白质组学用于识别耐药与父母HCC细胞中的差异蛋白质.
- 使用gefitinib进行EGFR抑制的体外和体内评估.
- 测试包括CCK-8,殖民地形成,细胞循环分析,西部涂抹和异种移植模型.
主要成果:
- 在获得的对regorafenib耐药HCC细胞中,EGFR表达显著增加.
- 格菲提尼布治疗恢复了耐药细胞和瘤对雷戈拉费尼布的敏感性.
- EGFR过度表达与RAS/RAF/P-ERK1/2通路激活相关.
结论:
- 通过RAS/RAF/ERK绕道激活,EGFR过度表达驱动HCC中获得的regorafenib耐药性.
- 用gefitinib抑制EGFR使HCC细胞对regorafenib重新敏感.
- 吉菲提尼布和雷戈拉费尼布的联合治疗显示了高级HCC的显著抗瘤潜力.
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