Fultang Livingstone, Gneo Luciana, De Santo Carmela, Mussai Francis J
Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.
Front Oncol. 2021 May 20;11:674720. doi: 10.3389/fonc.2021.674720. eCollection 2021.
Tumor cells require a higher supply of nutrients for growth and proliferation than normal cells. It is well established that metabolic reprograming in cancers for increased nutrient supply exposes a host of targetable vulnerabilities. In this article we review the documented changes in expression patterns of amino acid metabolic enzymes and transporters in myeloid malignancies and the growing list of small molecules and therapeutic strategies used to disrupt amino acid metabolic circuits within the cell. Pharmacological inhibition of amino acid metabolism is effective in inducing cell death in leukemic stem cells and primary blasts, as well as in reducing tumor burden in murine models of human disease. Thus targeting amino acid metabolism provides a host of potential translational opportunities for exploitation to improve the outcomes for patients with myeloid malignancies.
肿瘤细胞生长和增殖所需的营养供应比正常细胞更高。众所周知，癌症中为增加营养供应而进行的代谢重编程暴露了许多可靶向的脆弱点。在本文中，我们综述了髓系恶性肿瘤中氨基酸代谢酶和转运蛋白表达模式的已记录变化，以及用于破坏细胞内氨基酸代谢回路的小分子和治疗策略的不断增加的清单。氨基酸代谢的药理学抑制在诱导白血病干细胞和原代母细胞死亡以及减轻人类疾病小鼠模型中的肿瘤负担方面是有效的。因此，靶向氨基酸代谢为改善髓系恶性肿瘤患者的预后提供了许多潜在的转化利用机会。
