神经内分泌肿瘤（NET）是一组由神经内分泌细胞产生的肿瘤，常见于各种器官。相当一部分 NET 患者在确诊时已处于晚期或转移期。烷化剂是 NET 的主要治疗方法，O6-甲基鸟嘌呤甲基转移酶 (MGMT) 仍然是抵御这些药物引起的 DNA 损伤的第一道防线。临床试验表明，MGMT 启动子甲基化或其低/缺乏表达可以预测替莫唑胺在 NET 中的良好结果。它的状态可以帮助选择可以从烷化剂中受益的 NET 患者。因此，MGMT 状态可作为生物标志物，指导决定替莫唑胺作为个性化治疗选择的疗效。此外，深入研究 MGMT 状态的调节机制可以促进 MGMT 靶向疗法的开发，使 MGMT 表达水平高的个体受益。本综述旨在探讨 MGMT 调控的多态性并总结其在 NET 中的临床意义，这将有助于确立 MGMT 作为生物标志物的作用及其作为 NET 治疗靶点的潜力。此外，我们还探讨了在 MGMT 高甲基化亚组中联合替莫唑胺和免疫疗法的益处。未来的研究可以集中于优化替莫唑胺给药以诱导特定的免疫调节变化。版权所有 © 2024。由 Elsevier B.V. 出版。

Neuroendocrine tumors (NETs) are a diverse group of tumors that arise from neuroendocrine cells and are commonly found in various organs. A considerable proportion of NET patients were diagnosed at an advanced or metastatic stage. Alkylating agents are the primary treatment for NET, and O6-methylguanine methyltransferase (MGMT) remains the first-line of defense against DNA damage caused by these agents. Clinical trials have indicated that MGMT promoter methylation or its low/lacked expression can predict a favorable outcome with Temozolomide in NETs. Its status could help select NET patients who can benefit from alkylating agents. Therefore, MGMT status serves as a biomarker to guide decisions on the efficacy of Temozolomide as a personalized treatment option. Additionally, delving into the regulatory mechanisms of MGMT status can lead to the development of MGMT-targeted therapies, benefiting individuals with high levels of MGMT expression. This review aims to explore the polymorphism of MGMT regulation and summarize its clinical implications in NETs, which would help establish the role of MGMT as a biomarker and its potential as a therapeutic target in NETs. Additionally, we explore the benefits of combining Temozolomide and immunotherapy in MGMT hypermethylated subgroups. Future studies can focus on optimizing Temozolomide administration to induce specific immunomodulatory changes.Copyright © 2024. Published by Elsevier B.V.