Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.
Biotechnol Adv. 2012 Jan-Feb;30(1):30-51. doi: 10.1016/j.biotechadv.2011.07.006. Epub 2011 Jul 23.
Great interest is presently given to the analysis of metabolic changes that take place specifically in cancer cells. In this review we summarize the alterations in glycolysis, glutamine utilization, fatty acid synthesis and mitochondrial function that have been reported to occur in cancer cells and in human tumors. We then propose considering cancer as a system-level disease and argue how two hallmarks of cancer, enhanced cell proliferation and evasion from apoptosis, may be evaluated as system-level properties, and how this perspective is going to modify drug discovery. Given the relevance of the analysis of metabolism both for studies on the molecular basis of cancer cell phenotype and for clinical applications, the more relevant technologies for this purpose, from metabolome and metabolic flux analysis in cells by Nuclear Magnetic Resonance and Mass Spectrometry technologies to positron emission tomography on patients, are analyzed. The perspectives offered by specific changes in metabolism for a new drug discovery strategy for cancer are discussed and a survey of the industrial activity already going on in the field is reported.
目前人们对特定发生在癌细胞中的代谢变化分析非常感兴趣。在这篇综述中，我们总结了在癌细胞和人类肿瘤中报道的糖酵解、谷氨酰胺利用、脂肪酸合成和线粒体功能的改变。然后，我们提出将癌症视为一种系统水平的疾病，并论证了增强的细胞增殖和逃避细胞凋亡这两个癌症的标志性特征如何可以被评估为系统水平的特性，以及这种观点将如何改变药物发现。鉴于代谢分析对于研究癌细胞表型的分子基础和临床应用都非常重要，因此我们分析了用于此目的的更相关技术，包括细胞代谢组学和代谢通量分析的核磁共振和质谱技术，以及正电子发射断层扫描技术在患者中的应用。我们还讨论了代谢特定变化为癌症新药发现策略提供的前景，并报告了该领域已经开展的工业活动调查。
