Menin抑制剂治疗急性髓系白血病的研究进展

Research Progress of Menin Inhibitors in the Treatment of Acute Myeloid Leukemia

摘要: 急性髓系白血病是临床常见血液恶性肿瘤，KMT2A重排、NPM1突变亚型预后极差，且二者均依赖Menin-KMT2A致癌通路，这也为靶向治疗提供了突破口。Menin抑制剂可特异性阻断靶点结合，逆转异常转录程序，单药在复发难治性患者中展现出可观抗肿瘤活性，首款药物瑞维美尼已获批临床应用。但该类药物单药疗效有限、缓解周期短，耐药问题突出，联合用药成为提升疗效、克服耐药的核心策略，多项临床前及早期临床研究证实其与多种药物联用存在协同增效作用。目前Menin抑制剂耐药机制逐步明确，后续需深耕新一代药物研发、优化联合治疗方案，依托精准医学完善个体化治疗体系，进一步拓宽临床应用范围。

Abstract: Acute myeloid leukemia (AML) is a common hematological malignancy in clinical practice. The subtypes with KMT2A rearrangement or NPM1 mutation carry an extremely poor prognosis, and both subtypes are dependent on the oncogenic Menin-KMT2A pathway, which also provides a breakthrough for targeted therapy. Menin inhibitors can specifically block the binding of their targets and reverse abnormal transcriptional programs, and as monotherapies, they have demonstrated considerable anti-tumor activity in relapsed and refractory patients. Revumenib, the first such drug, has been approved for clinical application. However, these inhibitors have limitations as monotherapies, including limited efficacy, short remission duration and prominent drug resistance, making combination therapy a core strategy to improve efficacy and overcome drug resistance. A number of preclinical and early clinical studies have confirmed their synergistic effects when combined with various other drugs. At present, the mechanisms of resistance to Menin inhibitors are being gradually elucidated. In the future, it is necessary to devote greater efforts to the research and development of next-generation drugs, optimize combination therapy regimens, improve the individualized treatment system based on precision medicine, and further expand the scope of their clinical application.