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谷氨动力学是膀癌中新辅助化疗反应的潜在预测和治疗特征

YongHwan Kim¹, Hyein Ju¹, Seung-Yeon Yoo²

¹Department of Cell and Genetic Engineering, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.

Cell reports. Medicine

|October 5, 2023

概括

谷氨酸 (GSH) 途径失调导致肌肉侵入性膀癌 (MIBC) 中对新辅助化疗 (NAC) 的耐药性. 用西斯普拉丁向GSH动态提供了一个有希望的治疗策略,用于改善MIBC患者的NAC反应.

科学领域:

在瘤学瘤学.
生物化学生化学
遗传学是一个遗传学.

背景情况:

用新辅助化疗 (NAC) 进行激进囊切除术是肌肉侵入性膀癌 (MIBC) 的标准,但反应预测不佳.
目前的方法无法充分识别可能从NAC中受益的患者,因此需要新的预测生物标志物.
了解NAC耐药性的机制对于开发MIBC中有效的治疗策略至关重要.

研究的目的:

调查谷氨酸 (GSH) 途径在MIBC中调解对基于思普拉丁的NAC耐药性的作用.
在MIBC患者中确定与NAC反应和耐药性相关的分子标记物.
评估向GSH动态的治疗潜力,与MIBC治疗中西斯普拉丁结合使用.

主要方法:

多队列转录组分析以比较NAC敏感和耐药MIBC.
基于机器学习的瘤/肌瘤分类器用于数字化GSH动态蛋白质的免疫组织化学.
在实验室中对抗西斯普拉丁的MIBC细胞系研究和正位异种移植动物模型.

主要成果:

对GSH通路的调节失调是MIBC NAC抵抗的关键机制.
GSH代谢基因富含NAC耐性MIBC,而免疫反应基因富含NAC敏感MIBC.
包括谷氨酸酶-1在内的GSH动态蛋白与NAC耐药性有关,它们的调节与西斯普拉丁相结合,可在体内减少瘤生长.

结论:

在MIBC NAC抗性方面,GSH通路的失调是基本的.
在MIBC中,GSH动态蛋白质作为NAC反应的预测生物标志物.
针对GSH动态呈现了一个可行的治疗策略,以提高NAC在MIBC中的疗效.

关键词:

膀癌:膀癌是一种癌症.组合疗法治疗组合治疗.数字病理学数字病理学葡萄糖胺-1 酶-1 的作用.葡萄糖氨酸氨酸是什么?新辅助性化疗是一种新辅助性化疗.

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