文章：

脑转移的代谢适应

Metabolic adaptations of brain metastasis

原文发布日期：2025-07-24

DOI: 10.1038/s41568-025-00848-1

类型: Review Article

开放获取: 否

英文摘要：

Brain metastases remain a major clinical challenge, characterized by high mortality rates and often limited therapeutic options. The cellular and molecular processes that drive brain metastases are highly intricate, underscored by dynamic metabolic adaptations that enable tumour cells to thrive in the unique microenvironment of the brain. Emerging clinical and preclinical evidence reveals that these metabolic adaptations are not uniform but vary based on the tumour’s tissue of origin, oncogenomic landscape and capacity to endure nutrient stress. Notably, proliferative and dormant metastatic cells within the brain exhibit distinct metabolic profiles, highlighting the complexity of targeting these cells. Key metabolic pathways, including glucose, fatty acid and amino acid metabolism, are co-opted not only to sustain cancer cell survival and growth but also to modulate interactions with resident brain cells, reshaping their function to support metastasis. Importantly, this metabolic heterogeneity underscores the inadequacy of a one-size-fits-all therapeutic approach. Here, we review the adaptive metabolic reprogramming that facilitates brain metastases and discuss emerging strategies to tailor interventions aimed at preventing and treating overt brain metastases.

摘要翻译： 

脑转移仍然是一个主要的临床挑战，其特点是高死亡率且治疗选择往往有限。驱动脑转移的细胞和分子过程高度复杂，其核心是肿瘤细胞在独特大脑微环境中赖以存活的动态代谢适应。新出现的临床和临床前证据表明，这些代谢适应并非一成不变，而是根据肿瘤的组织起源、致癌基因组图谱及耐受营养胁迫的能力存在差异。值得注意的是，大脑内的增殖性和休眠性转移细胞表现出不同的代谢特征，这凸显了靶向这些细胞的复杂性。包括葡萄糖、脂肪酸和氨基酸代谢在内的关键代谢途径不仅被癌细胞利用以维持其生存和生长，还用于调节与常驻脑细胞的相互作用，从而重塑其功能以支持转移。重要的是，这种代谢异质性凸显了“一刀切”治疗方法的不足。本文回顾了促进脑转移的适应性代谢重编程，并讨论了定制干预措施以预防和治疗明显脑转移的新兴策略。

原文链接：

Metabolic adaptations of brain metastasis