瘤代谢可塑性治疗耐药性:从华堡效应到线粒体劫持
Yen-Dun Tony Tzeng1, Emmanuel Naveen Raj2, Shih-Hsuan Cheng2
1Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan.
Theranostics
|March 9, 2026
概括
癌症抗药性是由"代谢变形体" (耐药性持续细胞) 驱动的,这些细胞劫持了线粒体. 针对它们的代谢依赖和细胞间器官转移提供了新的治疗策略,以防止复发.
科学领域:
- 在瘤学瘤学.
- 癌症新陈代谢 癌症新陈代谢
- 细胞呼吸 细胞呼吸
背景情况:
- 对向癌症治疗的获得性耐药性是一个重大的临床挑战.
- 非遗传代谢重编程,而不仅仅是突变,驱动癌症细胞在治疗期间的生存.
- 耐药性持久细胞 (DTPs) 表现出代谢可塑性以逃避治疗.
研究的目的:
- 阐明"代谢变形体" (DTP) 的概念及其在获得抵抗中的作用.
- 审查DTPs使用的代谢适应,包括Warburg和反向Warburg效应.
- 突出细胞间器官转移的新机制及其对瘤免疫力的影响.
主要方法:
- 关于癌细胞代谢和耐药性的当前文献的综述.
- 对DTP代谢重编程的分析,包括葡萄糖和脂肪酸氧化中的转变.
- 通过道纳米管 (TNTs) 和线粒体劫持来检查"有机体寄生症".
主要成果:
- DTPs动态地切换代谢表型,从糖解转向氧化酸化 (OXPHOS).
- DTPs使用TNTs从免疫和树皮细胞中劫持功能性线粒体.
- 这种掠夺性行为会损害T细胞功能,促进免疫逃避,恢复瘤的呼吸能力.
结论:
- 代谢重编程和器官寄生是癌症耐药性的关键机制.
- 针对DTP线粒体依赖性和细胞间器官转移是一个有前途的治疗策略.
- 恢复免疫代谢与代谢向一起,可以消除DTP并防止复发.
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