Liang Liang, Luo Chen, Dong Shuo, Jia Zhe, Zhao Linyu, Tang Jingchao, Li Min, Zong Xiaoren, Li Simin, Ghani Zuryati Ab
School of Dental Sciences, Health Campus, Universiti Sains Malaysia, 16150, Kubang Kerian, Kelantan, Malaysia.
Department of Stomatology, Changzhi Medical College, Changzhi, 046000, Shanxi, China.
Discov Oncol. 2025 Aug 25;16(1):1613. doi: 10.1007/s12672-025-03299-0.
Oral cancer remains a significant global health challenge, with oral squamous cell carcinoma (OSCC) being the predominant histological type. Recent research has highlighted the critical role of metabolic reprogramming in oral carcinogenesis, particularly alterations in lipid homeostasis that contribute to disease progression and development. This review synthesizes current knowledge on lipid metabolism dysregulation in oral cancer, focusing on key aspects of metabolic reprogramming mechanisms, serum lipid profile alterations, lipid peroxidation pathways, immunometabolic interactions, and emerging therapeutic strategies. Mechanistically, OSCC exhibits significant alterations in key lipid metabolic enzymes, including upregulation of fatty acid synthase and ATP citrate lyase, and downregulation of carboxylesterase 2 (CES2), collectively promoting tumor growth and metastasis. These enzymatic changes are orchestrated through complex signaling pathways, notably the PI3K/AKT/mTOR axis, and manifest in altered membrane lipid composition, particularly within lipid microdomains that influence both cell signaling and drug resistance. Clinically, OSCC patients demonstrate characteristic serum lipid profile alterations, including reduced levels of total cholesterol, high-density lipoprotein cholesterol, and specific apolipoproteins, which show promise as non-invasive biomarkers for early detection and prognosis. Furthermore, enhanced lipid peroxidation through reactive oxygen species presents a double-edged sword in carcinogenesis, with oxidation products like malondialdehyde both contributing to mutagenesis and serving as potential diagnostic indicators. The complex interplay between lipid metabolism and tumor immunity, particularly through CD36 and sphingosine-1-phosphate signaling pathways, creates opportunities for immunometabolic interventions. Emerging therapeutic strategies targeting lipid metabolism include lipid-based nanoparticle drug delivery systems, metabolic enzyme inhibitors, and immunometabolic modulators, with promising preclinical results. Despite significant advances, challenges remain in translating these findings into clinical applications, necessitating further research on combination therapies, biomarker validation, and personalized treatment approaches. This comprehensive review provides valuable insights for both basic researchers and clinicians, potentially facilitating the development of novel diagnostic tools and therapeutic strategies for oral cancer management.
口腔癌仍然是一项重大的全球健康挑战，口腔鳞状细胞癌（OSCC）是主要的组织学类型。最近的研究突出了代谢重编程在口腔癌发生中的关键作用，特别是脂质稳态的改变，这有助于疾病的进展和发展。本综述综合了目前关于口腔癌脂质代谢失调的知识，重点关注代谢重编程机制、血清脂质谱改变、脂质过氧化途径、免疫代谢相互作用以及新兴治疗策略的关键方面。从机制上讲，OSCC在关键脂质代谢酶方面表现出显著改变，包括脂肪酸合酶和ATP柠檬酸裂解酶的上调，以及羧酸酯酶2（CES2）的下调，共同促进肿瘤生长和转移。这些酶的变化通过复杂的信号通路协调，特别是PI3K/AKT/mTOR轴，并表现为膜脂质组成的改变，特别是在影响细胞信号传导和耐药性的脂质微区内。临床上，OSCC患者表现出特征性的血清脂质谱改变，包括总胆固醇、高密度脂蛋白胆固醇和特定载脂蛋白水平降低，这些有望作为早期检测和预后的非侵入性生物标志物。此外，通过活性氧增强脂质过氧化在致癌过程中是一把双刃剑，丙二醛等氧化产物既有助于诱变，又可作为潜在的诊断指标。脂质代谢与肿瘤免疫之间的复杂相互作用，特别是通过CD36和鞘氨醇-1-磷酸信号通路，为免疫代谢干预创造了机会。针对脂质代谢的新兴治疗策略包括基于脂质的纳米颗粒药物递送系统、代谢酶抑制剂和免疫代谢调节剂，临床前结果很有前景。尽管取得了重大进展，但将这些发现转化为临床应用仍面临挑战，需要进一步研究联合疗法、生物标志物验证和个性化治疗方法。这篇全面的综述为基础研究人员和临床医生提供了有价值的见解，可能有助于开发用于口腔癌管理的新型诊断工具和治疗策略。
