饥饿癌细胞可以增强DNA损伤和免疫疗法反应
Aashirwad Shahi1, Dawit Kidane1
1Department of Physiology and Biophysics, College of Medicine, Howard University, Washington, DC 20059, USA.
Oncotarget
|June 20, 2024
概括
在前列腺癌 (PCa) 中使用cyst(e) 酶向囊代谢,会耗尽必需的氨基酸,诱导氧化应激和致癌细胞死亡的DNA损伤. 这种方法增强了高级PCa的其他疗法.
科学领域:
- 在瘤学瘤学.
- 代谢途径 代谢途径
- 生物化学 生化学
背景情况:
- 前列腺癌 (PCa) 带来了治疗挑战,特别是在转移性,抵抗割的阶段.
- 传统疗法由于毒性,耐药性和非目标效应而面临限制.
- PCa细胞表现出代谢的脆弱性,包括依赖非必需氨基酸,如氨酸.
研究的目的:
- 通过利用其代谢脆弱性来定义PCa的替代治疗策略.
- 调查囊酶在向氨酸代谢致癌细胞死亡方面的潜力.
- 探索囊酶与其他治疗剂的组合作用.
主要方法:
- 使用一种工程酶,cyst(e) inase,以耗尽细胞内氨酸和氨酸水平.
- 评估氨酸枯竭对反应性氧物种 (ROS) 生成和DNA损伤的影响.
- 评估cyst(e) inase与向抗氧化防御的药物 (例如,硫素) 的协同效应.
主要成果:
- 通过cyst(e) inase产生的囊氨酸枯竭会诱导PCa细胞中显著的氧化应激和DNA损伤.
- 升高的ROS度和破坏的谷氨合成有助于癌细胞死亡.
- 使用囊酶的组合疗法放大了细胞毒性,提高了治疗疗效.
结论:
- 向囊代谢是晚期前列腺癌的一个有前途的治疗策略.
- 囊酶介导的囊氨酸枯竭可以通过氧化应激和DNA损伤诱导癌细胞死亡.
- 这种方法有可能与DNA修复抑制剂和免疫检查点阻塞疗法结合使用.
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