Cancer cells demand amino acids beyond their usage as “building blocks” for protein synthesis. As a result, targeting amino acid acquisition and utilization has emerged as a pivotal strategy in cancer treatment. In the setting of leukemia therapy, compelling examples of targeting amino acid metabolism exist at both pre-clinical and clinical stages. This review focuses on summarizing novel insights into the metabolism of glutamine, asparagine, arginine, and tryptophan in leukemias, and providing a comprehensive discussion of perturbing their metabolism to improve the therapeutic outcomes. Certain amino acids, such as glutamine, play a vital role in the energy metabolism of cancer cells and the maintenance of redox balance, while others, such as arginine and tryptophan, contribute significantly to the immune microenvironment. Therefore, assessing the efficacy of targeting amino acid metabolism requires comprehensive strategies. Combining traditional chemotherapeutics with novel strategies to perturb amino acid metabolism is another way to improve the outcome in leukemia patients via overcoming chemo-resistance or promoting immunotherapy. In this review, we also discuss several ongoing or complete clinical trials, in which targeting amino acid metabolism is combined with other chemotherapeutics in treating leukemia.
癌细胞对氨基酸的需求已超越其作为蛋白质合成"原料"的传统功能。因此，靶向氨基酸的获取与利用已成为癌症治疗的关键策略。在白血病治疗领域，靶向氨基酸代谢的疗法在临床前及临床阶段均已展现出显著成效。本综述重点总结白血病中谷氨酰胺、天冬酰胺、精氨酸和色氨酸代谢机制的新发现，系统探讨通过干预这些氨基酸代谢以改善治疗效果的策略。某些氨基酸（如谷氨酰胺）在癌细胞能量代谢和氧化还原平衡维持中发挥关键作用，而另一些氨基酸（如精氨酸和色氨酸）则对免疫微环境具有重要调控功能。因此，评估靶向氨基酸代谢的疗效需要采用综合策略。将传统化疗药物与新型氨基酸代谢干预策略相结合，通过克服化疗耐药或促进免疫治疗，成为改善白血病患者预后的新途径。本综述还讨论了多项正在进行或已完成的临床试验，这些研究将靶向氨基酸代谢与其他化疗药物联合应用于白血病治疗。
Enhancing Leukemia Treatment: The Role of Combined Therapies Based on Amino Acid Starvation
肿瘤(癌症)患者之家