使用稳定同位素分析癌症患者代谢途径

SCI

16 November 2023

Metabolic pathway analysis using stable isotopes in patients with cancer

(Nature Reviews Cancer, IF: 78.5)

• Caroline R. Bartman1,4, Brandon Faubert 2,4, Joshua D. Rabinowitz 1,5 & Ralph J. DeBerardinis

• CORRESPONDENCE TO: joshr@princeton.edu; ralph.deberardinis@utsouthwestern.edu

Abstract 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.

代谢重编码是恶性转化和癌细胞生长的关键。肿瘤如何利用营养物质以及重编码途径的相对速率是人们极为关注的领域。肿瘤代谢是由癌细胞内在和外在因素的复杂和未完全定义的组合决定的。这种复杂性增加了包括在癌症患者中评估癌症代谢在疾病相关微环境中的价值。稳定同位素示踪是探测体内肿瘤代谢的一种信息丰富、用途广泛的方法。它已被广泛应用于癌症的临床前模型中，并且在癌症患者中的应用频率越来越高。在这篇综述中，我们描述了使用体内同位素示踪来定义肿瘤中的营养偏好和通路参与的方法，以及这项工作中浮现的一些原则。迄今为止报道的稳定同位素输注显示，在人类中，肿瘤使用多种营养物质来供应中心代谢途径，包括三羧酸循环和氨基酸合成。新兴数据表明，稳定同位素示踪检测到的一些活动与不良临床结果相关，并可能导致癌症进展。我们还讨论了同位素示踪方面的当前挑战，包括体内和体外模型的比较，以及未来在肿瘤代谢中存在新发现的机会。

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