文章：

利用稳定同位素分析癌症患者的代谢途径

Metabolic pathway analysis using stable isotopes in patients with cancer

原文发布日期：2023-10-31

DOI: 10.1038/s41568-023-00632-z

类型: Review Article

开放获取: 否

英文摘要：

Metabolic reprogramming is central to malignant transformation and cancer cell growth. How tumours use nutrients and the relative rates of reprogrammed pathways are areas of intense investigation. Tumour metabolism is determined by a complex and incompletely defined combination of factors intrinsic and extrinsic to cancer cells. This complexity increases the value of assessing cancer metabolism in disease-relevant microenvironments, including in patients with cancer. Stable-isotope tracing is an informative, versatile method for probing tumour metabolism in vivo. It has been used extensively in preclinical models of cancer and, with increasing frequency, in patients with cancer. In this Review, we describe approaches for using in vivo isotope tracing to define fuel preferences and pathway engagement in tumours, along with some of the principles that have emerged from this work. Stable-isotope infusions reported so far have revealed that in humans, tumours use a diverse set of nutrients to supply central metabolic pathways, including the tricarboxylic acid cycle and amino acid synthesis. Emerging data suggest that some activities detected by stable-isotope tracing correlate with poor clinical outcomes and may drive cancer progression. We also discuss current challenges in isotope tracing, including comparisons of in vivo and in vitro models, and opportunities for future discovery in tumour metabolism.

摘要翻译： 

代谢重编程是恶性转化和癌细胞生长的核心。肿瘤如何利用营养物质以及重编程途径的相对速率是当前研究的热点领域。肿瘤代谢由癌细胞内外因素复杂且尚未完全明确的组合所决定。这种复杂性提升了在疾病相关微环境（包括癌症患者体内）评估癌症代谢的价值。稳定同位素示踪是一种信息丰富、用途广泛的体内肿瘤代谢探测方法，已广泛应用于临床前癌症模型，并越来越多地应用于癌症患者。本篇综述中，我们阐述了利用体内同位素示踪技术界定肿瘤燃料偏好和通路参与的方法，以及由此揭示的部分生物学规律。目前已报道的稳定同位素输注实验表明，在人体内肿瘤利用多种营养物质来支撑核心代谢途径，包括三羧酸循环和氨基酸合成。新出现的数据表明，通过稳定同位素示踪检测到的某些代谢活性与不良临床结局相关，并可能驱动癌症进展。我们还将讨论同位素示踪当前面临的挑战（包括体内外模型的比较）以及未来在肿瘤代谢领域的探索机遇。

原文链接：

Metabolic pathway analysis using stable isotopes in patients with cancer