Yabushita Tomohiro, Goyama Susumu
International Research Center for Medical Sciences, Kumamoto University, Kumamoto, Japan.
Division of Molecular Oncology, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Japan.
Exp Hematol. 2025 Feb;142:104693. doi: 10.1016/j.exphem.2024.104693. Epub 2024 Dec 6.
Nucleic acid analogs, including cytarabine, decitabine, and azacitidine, have significantly advanced therapeutic approaches for myeloid tumors over the past five decades. Nucleic acid metabolism is a crucial pathway driving myeloid tumorigenesis, with emerging evidence indicating that myeloid tumors are particularly dependent on the de novo nucleotide synthesis pathway, underscoring its potential as a therapeutic target. This review provides a comprehensive overview of nucleic acid metabolism, focusing on de novo nucleotide synthesis. We then described the range of clinically utilized agents targeting nucleic acid metabolism and discussed our recent findings on the nonepigenetic actions of decitabine, as well as the therapeutic effects of inosine monophosphate dehydrogenase (IMPDH) inhibitors in the treatment of myeloid tumors.
在过去的五十年里，包括阿糖胞苷、地西他滨和阿扎胞苷在内的核酸类似物显著推进了髓系肿瘤的治疗方法。核酸代谢是驱动髓系肿瘤发生的关键途径，新出现的证据表明髓系肿瘤特别依赖于从头合成核苷酸途径，这突出了其作为治疗靶点的潜力。本综述全面概述了核酸代谢，重点是从头合成核苷酸。然后我们描述了临床上使用的针对核酸代谢的药物范围，并讨论了我们最近关于地西他滨非表观遗传作用的发现，以及肌苷单磷酸脱氢酶（IMPDH）抑制剂在治疗髓系肿瘤中的疗效。
