Advances in Understanding of Metabolism of B-Cell Lymphoma: Implications for Therapy

谷氨酰胺分解 PI3K/AKT/mTOR通路 代谢途径 生物 生发中心 癌症研究 癌细胞 氧化磷酸化 癌症 信号转导 细胞生物学 生物化学 新陈代谢 B细胞 遗传学 抗体
作者
Katarína Kľučková,Annalisa D’Avola,John C. Riches
出处
期刊:Cancers [Multidisciplinary Digital Publishing Institute]
卷期号:14 (22): 5552-5552 被引量:9
标识
DOI:10.3390/cancers14225552
摘要

There have been significant recent advances in the understanding of the role of metabolism in normal and malignant B-cell biology. Previous research has focused on the role of MYC and mammalian target of rapamycin (mTOR) and how these interact with B-cell receptor signaling and hypoxia to regulate glycolysis, glutaminolysis, oxidative phosphorylation (OXPHOS) and related metabolic pathways in germinal centers. Many of the commonest forms of lymphoma arise from germinal center B-cells, reflecting the physiological attenuation of normal DNA damage checkpoints to facilitate somatic hypermutation of the immunoglobulin genes. As a result, these lymphomas can inherit the metabolic state of their cell-of-origin. There is increasing interest in the potential of targeting metabolic pathways for anti-cancer therapy. Some metabolic inhibitors such as methotrexate have been used to treat lymphoma for decades, with several new agents being recently licensed such as inhibitors of phosphoinositide-3-kinase. Several other inhibitors are in development including those blocking mTOR, glutaminase, OXPHOS and monocarboxylate transporters. In addition, recent work has highlighted the importance of the interaction between diet and cancer, with particular focus on dietary modifications that restrict carbohydrates and specific amino acids. This article will review the current state of this field and discuss future developments.
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