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患者瘤和匹配的异种移植之间代谢表型的保存和分歧

Aparna D Rao^1,2,3, Ling Cai^1,4, Marelize Snyman⁵

¹Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Nature metabolism

|July 30, 2025

概括

与患者的黑色素瘤相比,患者衍生异端移植 (PDX) 显示了代谢上的相似性和差异. 大多数PDX保留了持久的代谢指纹,为癌症代谢研究提供了宝贵的资源.

科学领域:

在瘤学瘤学.
代谢学代谢学代谢学
临床前癌症模型

背景情况:

患者衍生异种移植 (PDX) 是广泛使用的临床前癌症模型.
它们准确反映患者瘤代谢的能力尚未完全理解.

研究的目的:

为了比较患者黑色素瘤的代谢概况及其匹配的PDXs.
在PDX模型中评估瘤代谢的忠实性.

主要方法:

为[U-¹³C]葡萄糖追踪和代谢学分析开发了一个并行工作流.
分析了患者黑色素瘤和相应的PDXs的样本.

主要成果:

患有黑色素瘤的患者表现出显著的TCA循环标记,与人类大脑瘤相当.
与患者瘤相比,PDXs显示了类似的TCA循环标记,但具有更高的甘油性代谢物标记.
代谢学揭示了由于物种特定因素导致的~100个一致的代谢物变化.
大多数PDX在通道上保持了稳定的"代谢指纹",可追溯到原始瘤.

结论:

PDX模型部分回顾了患者的黑色素瘤新陈代谢,在糖解中存在显著差异.
特定物种因素显著影响PDXs中的代谢物概况.
PDXs提供了一个很长时间的代谢指纹,对癌症代谢研究很有用.

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