Unraveling the mysteries of MGMT: Implications for neuroendocrine tumors

IF 9.7 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochimica et biophysica acta. Reviews on cancer Pub Date : 2024-09-18 DOI:10.1016/j.bbcan.2024.189184
Jianyun Jiang , Junfeng Xu , Shunrong Ji , Xianjun Yu , Jie Chen
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Abstract

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.
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揭开 MGMT 的神秘面纱:对神经内分泌肿瘤的影响。
神经内分泌肿瘤(NET)是一类由神经内分泌细胞引起的多种肿瘤,常见于各种器官。相当一部分NET患者被诊断为晚期或转移期。烷化剂是治疗 NET 的主要药物,而 O6-甲基鸟嘌呤甲基转移酶(MGMT)仍然是抵御这些药物造成的 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/缺乏表达可预测替莫唑胺治疗 NET 的良好疗效。它的状态有助于筛选出能从烷化剂中获益的 NET 患者。因此,MGMT 状态可作为一种生物标志物,指导替莫唑胺作为一种个性化治疗方案的疗效决策。此外,深入研究 MGMT 状态的调控机制可以开发 MGMT 靶向疗法,使高水平 MGMT 表达的个体受益。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使用替莫唑胺和免疫疗法的益处。未来的研究可侧重于优化替莫唑胺的用药,以诱导特定的免疫调节变化。
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来源期刊
Biochimica et biophysica acta. Reviews on cancer
Biochimica et biophysica acta. Reviews on cancer 医学-生化与分子生物学
CiteScore
17.20
自引率
0.00%
发文量
138
审稿时长
33 days
期刊介绍: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer encompasses the entirety of cancer biology and biochemistry, emphasizing oncogenes and tumor suppressor genes, growth-related cell cycle control signaling, carcinogenesis mechanisms, cell transformation, immunologic control mechanisms, genetics of human (mammalian) cancer, control of cell proliferation, genetic and molecular control of organismic development, rational anti-tumor drug design. It publishes mini-reviews and full reviews.
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