缺氧诱导因子介导肝细胞癌对酪氨酸激酶抑制剂耐药的机制及应对策略 点击下载
论文标题: | 缺氧诱导因子介导肝细胞癌对酪氨酸激酶抑制剂耐药的机制及应对策略 |
英文标题: | |
中文摘要: | 酪氨酸激酶抑制剂(TKI)的应用是肝细胞癌系统治疗的重要进展,但由于其持续的抗血管生成治疗会导致肿瘤缺氧增加,加速缺氧微环境的发展,促进缺氧诱导因子(HIF)表达,进而导致肿瘤患者对TKI耐药。本文从代谢重编程、癌及癌相关基因的异常表达、铁死亡等方面总结了HIF介导肝细胞癌对TKI耐药的作用机制,并归纳耐药应对策略,以期为临床解决TKI耐药问题提供参考。结果发现,HIF/糖酵解轴抑制剂(如异黄酮染料木素、辛伐他汀等)可基于代谢重编程机制改善TKI耐药,癌基因靶向抑制剂和TKI的联合应用(如辣椒素和索拉非尼联合)可基于癌及癌相关基因的异常表达机制改善TKI耐药,脂肪酸合酶抑制剂(如奥利司他)可基于铁死亡机制改善TKI耐药。 |
英文摘要: | The use of tyrosine kinase inhibitors (TKI) has been an important advance in the systemic treatment of hepatocellular carcinoma, but their sustained anti-angiogenic therapy leads to increased tumor hypoxia, accelerates the development of a hypoxic microenvironment and promotes the expressions of hypoxia-inducible factors (HIF), thereby inducing drug resistance of tumor patients to TKI. This paper summarizes the mechanism of action of HIF mediating TKI resistance in hepatocellular carcinoma in aspects of metabolic reprogramming, abnormal expressions of cancer and cancer-associated genes, and ferroptosis, and sorts resistance response strategies to provide reference for clinical solutions to TKI resistance issues. As results show, HIF/ glycolysis axis inhibitors (isoflavonoid genistein, simvastatin, etc.) can improve TKI resistance based on metabolic reprogramming mechanism; oncogene-targeted inhibitors combined with TKI (the combination of capsaicin and sorafenib) can improve TKI resistance based on abnormal expression of cancer and cancer-related genes; fatty acid synthase inhibitor (orlistat) can improve TKI resistance based on ferroptosis mechanism. |
期刊: | 2024年第35卷第10期 |
作者: | 葛晓英;郑丹;江雪;鲍蕾蕾;卞俊 |
英文作者: | GE Xiaoying,ZHENG Dan,JIANG Xue,BAO Leilei,BIAN Jun |
关键字: | 肝细胞癌;酪氨酸激酶抑制剂;耐药;缺氧诱导因子 |
KEYWORDS: | hepatocellular carcinoma; tyrosine kinase inhibitors; drug resistance; hypoxia-inducible factor |
总下载数: | 81次 |
本日下载数: | 2次 |
本月下载数: | 81次 |
文件大小: | 619.60Kb |
* 注:未经本站明确许可,任何网站不得非法盗链资源下载连接及抄袭本站原创内容资源!在此感谢您的支持与合作!