王 君,王唯静,许 悦,陈云丽,乔玉莉

MDM2与MDMX（MDM4）是p53肿瘤抑制通路的关键负调控因子，其功能失调与多种恶性肿瘤的发生发展密切相关。MDM2/MDMX的经典致癌途径包括基因扩增、单核苷酸多态性（SNP）和转录后修饰导致过度表达，进而抑制p53功能，此外，MDM2/MDMX还存在不依赖于p53的促癌功能，如调控细胞周期、凋亡抵抗、诱导基因组不稳定性和上皮-间质转化（EMT）。再者，可变剪接产生的异构体以及它们与核糖体应激通路的交互作用，进一步增加了其功能的复杂性。鉴于MDM2/MDMX在众多表达野生型p53的癌症中过表达，它们已成为极具潜力的肿瘤生物标志物和治疗靶点。目前，以Nutlins为代表的小分子抑制剂、肽类拮抗剂等靶向干预策略已进入临床研究阶段。未来，深入解析其组织特异性功能、异构体表达谱以及与突变型p53的相互作用，将推动更精准的诊断和联合治疗策略的发展。本文系统综述了MDM2/MDMX的分子结构、其与p53构成的复杂调控网络，以及它们在癌症中的异常激活机制。

MDM2；MDMX；p53；癌症；靶向治疗

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