Chen Xinyi, Yang Mu, Wang Lu, Tu Jingyao, Yuan Xianglin
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Int J Med Sci. 2025 Jun 9;22(11):2852-2876. doi: 10.7150/ijms.108549. eCollection 2025.
Metabolic reprogramming enables cancer cells to adapt to the tumor microenvironment, facilitating their survival, proliferation, and resistance to therapy. While glucose has long been considered the primary substrate for cancer cell metabolism, recent studies have highlighted the role of fructose as an alternative carbon source. Fructose metabolism, particularly through key enzymes such as ketohexokinase (KHK) and aldolase B (ALDOB), along with the fructose transporter GLUT5, supports tumor growth, metastasis, and therapeutic resistance. This review explores the mechanisms by which fructose metabolism influences cancer progression, focusing on its metabolic pathways and its impact on the tumor microenvironment. By promoting glycolysis, lipid biosynthesis, and nucleotide production, fructose metabolism enhances the metabolic adaptability of cancer cells, especially in glucose-deprived conditions. A comprehensive understanding of these processes offers potential insights into therapeutic strategies targeting fructose metabolism for cancer treatment. However, further studies are required to fully elucidate the complex role of fructose in various malignancies.
代谢重编程使癌细胞能够适应肿瘤微环境，促进其存活、增殖以及对治疗的抵抗。长期以来，葡萄糖一直被视为癌细胞代谢的主要底物，但最近的研究突出了果糖作为替代碳源的作用。果糖代谢，特别是通过关键酶如己酮糖激酶（KHK）和醛缩酶B（ALDOB），以及果糖转运体GLUT5，支持肿瘤生长、转移和治疗抵抗。本综述探讨果糖代谢影响癌症进展的机制，重点关注其代谢途径及其对肿瘤微环境的影响。通过促进糖酵解、脂质生物合成和核苷酸生成，果糖代谢增强了癌细胞的代谢适应性，尤其是在葡萄糖缺乏的条件下。全面了解这些过程为针对果糖代谢的癌症治疗策略提供了潜在的见解。然而，需要进一步研究以充分阐明果糖在各种恶性肿瘤中的复杂作用。
