Cai Hong, Zhang Feng, Xu Fang, Yang Chunhui
Department of Clinical Laboratory, The Second Hospital of Dalian Medical University, Dalian, Liaoning, China.
Department of Clinical Laboratory, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China.
Front Oncol. 2025 May 21;15:1564226. doi: 10.3389/fonc.2025.1564226. eCollection 2025.
Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide. Recent advancements have illuminated the intricate metabolic reprogramming that underpins NSCLC progression and resistance to therapy. Beyond the classical Warburg effect, emerging evidence highlights the pivotal roles of altered lipid metabolism, amino acid utilization, and the metabolic crosstalk within the tumor microenvironment (TME). This review delves into the latest discoveries in NSCLC metabolism, emphasizing novel pathways and mechanisms that contribute to tumor growth and survival. We critically assess the interplay between cancer cell metabolism and the TME, explore the impact of metabolic heterogeneity, and discuss how metabolic adaptations confer therapeutic resistance. By integrating insights from cutting-edge technologies such as single-cell metabolomics and spatial metabolomics, we identify potential metabolic vulnerabilities in NSCLC. Finally, we propose innovative therapeutic strategies that target these metabolic dependencies, including combination approaches that enhance the efficacy of existing treatments and pave the way for personalized metabolic therapies.
非小细胞肺癌（NSCLC）仍然是全球癌症相关死亡的主要原因。最近的进展揭示了复杂的代谢重编程，这种重编程是NSCLC进展和对治疗产生耐药性的基础。除了经典的瓦伯格效应，新出现的证据突出了脂质代谢改变、氨基酸利用以及肿瘤微环境（TME）内代谢串扰的关键作用。本综述深入探讨了NSCLC代谢的最新发现，强调了有助于肿瘤生长和存活的新途径和机制。我们批判性地评估癌细胞代谢与TME之间的相互作用，探讨代谢异质性的影响，并讨论代谢适应如何赋予治疗耐药性。通过整合来自单细胞代谢组学和空间代谢组学等前沿技术的见解，我们确定了NSCLC中潜在的代谢脆弱性。最后，我们提出了针对这些代谢依赖性的创新治疗策略，包括增强现有治疗效果并为个性化代谢疗法铺平道路的联合方法。
