利用代谢组学监测抗癌药物。

Y-L Chung, J R Griffiths
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引用次数: 26

摘要

在抗癌药物起作用后,癌细胞的代谢组可能会发生变化。这些变化可以用来决定是否继续治疗,或者在药物试验的背景下,表明药物是否有效,也许是其作用机制。核磁共振波谱(NMR/MRS)方法可以为新的抗癌药物提供重要的见解,以加速药物开发过程,包括药物对其作用部位(称为药效学)的影响的时间过程研究,在这种情况下是癌症。此外,目前正在开发的某些类型的抗癌药物(例如抗血管生成药物)被设计为与其他药物联合使用,并且在1期临床试验中作为单一药物使用时不会引起肿瘤缩小。因此,核磁共振/MRS可能在早期临床试验中监测此类药物的药效学作用方面具有特殊作用。本文综述了利用体外核磁共振和体内核磁共振技术监测一些新型抗癌药物对肿瘤代谢组的影响。离体核磁共振方法是对体内测量的补充,因为它们可以提供额外的信息,并有助于解释体内数据。
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Using metabolomics to monitor anticancer drugs.

The metabolome of a cancer cell is likely to show changes after responding to an anticancer drug. These changes could be used to decide whether to continue treatment or, in the context of a drug trial, to indicate whether the drug is working and perhaps its mechanism of action. (Nuclear) magnetic resonance spectroscopy (NMR/MRS) methods can offer important insights into novel anticancer agents in order to accelerate the drug development process including time-course studies on the effect of a drug on its site of action (termed pharmacodynamics), in this case the cancer. In addition, some classes of anticancer agents currently under development (e.g. antiangiogenics) are designed to be used in combination with other drugs and will not cause tumour shrinkage when used as single agents in Phase 1 clinical trials. Thus NMR/MRS may have a special role in monitoring the pharmacodynamic actions of such drugs in early-phase clinical trials. This review focuses on the use of ex vivo NMR and in vivo MRS methods for monitoring the effect of some novel anticancer drugs on the cancer metabolome. Ex vivo NMR methods are complementary to in vivo measurements, as they can provide additional information and help in the interpretation of the in vivo data.

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