地西他滨和 5-氮杂胞苷等 DNA 低甲基化剂 (HMA) 已在骨髓增生异常综合征和急性髓性白血病的治疗范例中发挥作用，它们被认为通过恢复抑癌基因的表达来发挥抗癌作用。由于其相对有利的不良反应特征和已知的穿过血脑屏障的能力，其在治疗胶质母细胞瘤（GBM）和其他中枢神经系统恶性肿瘤中的应用正在积极研究中。本综述探讨了目前可用的 HMA 类型、其已知和不太了解的抗肿瘤机制，以及迄今为止其在胶质母细胞瘤和其他实体恶性肿瘤中的临床前和临床疗效的证据。本综述讨论了 HMA 与现有和新兴 GBM 治疗方法（包括替莫唑胺、免疫检查点抑制剂和癌症疫苗）可能具有的潜在协同作用。总结了最近在新诊断和复发性 GBM 临床试验中的成功和挫折，以强调 HMA 改善治疗反应的机会。还评估了未来临床试验的挑战。版权所有：© 2024 Silva-Hurtado 等人。

DNA hypomethylating agents (HMAs) such as decitabine and 5-azacytidine have established roles in the treatment paradigms for myelodysplastic syndrome and acute myelogenous leukemia, where they are considered to exert their anticancer effects by restoring the expression of tumor suppressor genes. Due to their relatively favorable adverse effect profile and known ability to pass through the blood-brain barrier, applications in the treatment of glioblastoma (GBM) and other central nervous system malignancies are under active investigation. The present review examines the types of HMAs currently available, their known and less-understood antineoplastic mechanisms, and the evidence to date of their preclinical and clinical efficacy in glioblastoma and other solid malignancies. The present review discusses the potential synergies HMAs may have with established and emerging GBM treatments, including temozolomide, immune checkpoint inhibitors and cancer vaccines. Recent successes and setbacks in clinical trials for newly diagnosed and recurrent GBM are summarized in order to highlight opportunities for HMAs to improve therapeutic responses. Challenges for future clinical trials are also assessed.Copyright: © 2024 Silva-Hurtado et al.