文章：

核苷酸代谢：一种泛癌症代谢依赖性

Nucleotide metabolism: a pan-cancer metabolic dependency

原文发布日期：2023-03-27

DOI: 10.1038/s41568-023-00557-7

类型: Review Article

开放获取: 否

英文摘要：

Metabolic alterations are a key hallmark of cancer cells, and the augmented synthesis and use of nucleotide triphosphates is a critical and universal metabolic dependency of cancer cells across different cancer types and genetic backgrounds. Many of the aggressive behaviours of cancer cells, including uncontrolled proliferation, chemotherapy resistance, immune evasion and metastasis, rely heavily on augmented nucleotide metabolism. Furthermore, most of the known oncogenic drivers upregulate nucleotide biosynthetic capacity, suggesting that this phenotype is a prerequisite for cancer initiation and progression. Despite the wealth of data demonstrating the efficacy of nucleotide synthesis inhibitors in preclinical cancer models and the well-established clinical use of these drugs in certain cancer settings, the full potential of these agents remains unrealized. In this Review, we discuss recent studies that have generated mechanistic insights into the diverse biological roles of hyperactive cancer cell nucleotide metabolism. We explore opportunities for combination therapies that are highlighted by these recent advances and detail key questions that remain to be answered, with the goal of informing urgently warranted future studies.

摘要翻译： 

代谢改变是癌细胞的一个关键特征，而三磷酸核苷合成与利用的增强是不同癌症类型和遗传背景中癌细胞普遍存在的重要代谢依赖性。癌细胞的许多侵袭性行为，包括不受控制的增殖、化疗耐药、免疫逃逸和转移，都在很大程度上依赖于增强的核苷酸代谢。此外，大多数已知的致癌驱动因素会上调核苷酸生物合成能力，表明这种表型是癌症发生和发展的先决条件。尽管大量数据证明了核苷酸合成抑制剂在临床前癌症模型中的功效，并且这些药物在某些癌症治疗中的临床应用已得到确认，但这些药物的全部潜力仍未得到充分发挥。在本篇综述中，我们讨论了近期对高活性癌细胞核苷酸代谢多样化生物学作用产生机制性见解的研究。我们探索这些最新进展所揭示的联合治疗机遇，并详细阐述亟待解决的关键问题，旨在为未来亟需开展的研究提供参考。

原文链接：

Nucleotide metabolism: a pan-cancer metabolic dependency