NMR-based metabolomics: translational application and treatment of cancer.
NMR-based metabolomics: translational application and treatment of cancer.
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发表时间：
2007-12
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通讯作者：
N. Serkova;J. Spratlin;S. Eckhardt
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作者：
N. Serkova;J. Spratlin;S. Eckhardt
癌细胞具有高度独特的代谢表型，其特征在于高葡萄糖摄取、增加的糖酵解活性、降低的线粒体活性、低生物能量消耗和增加的磷脂周转。除了这些恶性肿瘤的一般代谢标志物外，组织特异性生物化学还鉴定了在特定肿瘤类型中发现的特异性内源性代谢物。这些包括神经母细胞瘤中的N-乙酰天冬氨酸，神经胶质瘤中的肌醇和前列腺癌中的柠檬酸盐。代谢谱可以很容易地进行评估，以监测对新型靶向药物的反应性和耐药性的发展，例如，在发生细胞抑制作用而不是细胞毒性的情况下。利用现代分析技术与统计方法相结合，开发了一种称为“代谢组学”的方法。代谢组学已用于生成患者样本的总体代谢谱，然后可用于确定治疗反应。本文综述了现有的基于核磁共振的方法，在组织活检和体液中的全球代谢分析和使用非侵入性放射技术来评估代谢生物标志物。此外，对新型靶向药物（包括酪氨酸激酶抑制剂和代谢调节剂）的代谢反应研究进行了评价。
Cancer cells possess a highly unique metabolic phenotype which is characterized by high glucose uptake, increased glycolytic activity, decreased mitochondrial activity, low bioenergetic expenditure and increased phospholipid turnover. In addition to these general metabolic markers of malignancy, tissue-specific biochemistry has identified specific endogenous metabolites found in particular tumors types. These include N-acetyl aspartate in neuroblastoma, myo-inositol in gliomas and citrate in prostate cancer. Metabolic profiles can be readily assessed to monitor responsiveness and the development of resistance to novel targeted drugs, for example, where a cytostatic effect rather than cytotoxicity occurs. Using modern analytical technologies in combination with statistical approaches, a methodology termed 'metabolomics' has been developed. Metabolomics has been used to generate a global metabolic profile on patient samples, which can then be used to determine treatment response. This review describes existing NMR-based approaches for global metabolic profiling in tissue biopsies and body fluids and the use of non-invasive radiological techniques to assess metabolic biomarkers. In addition, studies on metabolic responses to novel targeted drugs, including tyrosine kinase inhibitors and metabolic modulators, are evaluated.