Ohshima Kenji
Department of Molecular Pathology, Faculty of Medicine, Hyogo Medical University, Nishinomiya, Japan.
Pathol Int. 2025 Aug;75(8):387-402. doi: 10.1111/pin.70034. Epub 2025 Jun 24.
Cancer cells reprogram their metabolism during progression to adapt to the tumor microenvironment, which is characterized by distinct differences in nutrient availability, oxygen concentrations, and acidity. This metabolic reprogramming can simultaneously create metabolic vulnerabilities unique to cancer cells, making cancer metabolism a promising therapeutic target. Since the clinical application of folate antimetabolites in the 1940s, numerous therapeutic strategies targeting cancer metabolism have been developed. In recent years, advancements in technologies such as metabolome analysis have facilitated the development of agents that more specifically target cancer cell metabolism. However, these newly developed agents often face challenges in demonstrating efficacy as monotherapies in clinical trials. Nevertheless, combination therapies, designed based on precise mechanistic insights and incorporating agents such as immune-checkpoint and signaling-pathway inhibitors, have shown promising efficacy. This review provides an overview of the current landscape of therapeutic strategies targeting cancer metabolism, with a particular focus on approaches targeting amino acid, fatty acid, and glucose metabolism in cancer cells.
癌细胞在进展过程中会重新编程其代谢，以适应肿瘤微环境，该环境的特征是营养物质可用性、氧浓度和酸度存在明显差异。这种代谢重编程可同时产生癌细胞特有的代谢脆弱性，使癌症代谢成为一个有前景的治疗靶点。自20世纪40年代叶酸抗代谢物临床应用以来，已开发出众多针对癌症代谢的治疗策略。近年来，代谢组分析等技术的进步推动了更特异性靶向癌细胞代谢的药物的开发。然而，这些新开发的药物在临床试验中作为单一疗法证明疗效时往往面临挑战。尽管如此，基于精确的机制见解设计并纳入免疫检查点和信号通路抑制剂等药物的联合疗法已显示出有前景的疗效。本综述概述了目前针对癌症代谢的治疗策略格局，特别关注针对癌细胞中氨基酸、脂肪酸和葡萄糖代谢的方法。
