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塞利尼索在急性髓系白血病中的应用:治疗作用与当前挑战

Selinexor in acute myeloid leukemia: therapeutic applications and current challenges.

作者信息

Qie Ziyu, Ma Li, Tan Jie, Peng Xiaochun

机构信息

Department of Hematology, The First Affiliated Hospital of Yangtze University, Jingzhou, China.

Department of Gastroenterology, Jianli People's Hospital, Jingzhou, China.

出版信息

Front Pharmacol. 2025 May 20;16:1602911. doi: 10.3389/fphar.2025.1602911. eCollection 2025.

Abstract

This article aims to review the current application status and research advancements of selinexor in the treatment of acute myeloid leukemia (AML). Selinexor, as the first oral selective inhibitor of nuclear export protein Exportin-1 (XPO1), inhibits the abnormal nuclear export of tumor suppressor proteins by blocking XPO1, thereby restoring their activity and exerting antitumor effects. Clinical studies have shown that selinexor monotherapy or combination therapy has demonstrated good anti-leukemia effects in AML, especially in patients with relapsed/refractory AML. In addition, the combination of selinexor with other drugs, such as demethylating agents and FLT3 inhibitors, has shown synergistic antitumor effects. Although selinexor has shown potential, its resistance and adverse reactions still need further research and control. Future research directions include exploring the best medication schemes, clarifying the appropriate population, and developing new combination treatment plans to improve treatment effects and overcome drug resistance issues.

摘要

本文旨在综述塞利尼索在急性髓系白血病(AML)治疗中的应用现状及研究进展。塞利尼索作为首个口服选择性核输出蛋白Exportin-1(XPO1)抑制剂,通过阻断XPO1抑制肿瘤抑制蛋白的异常核输出,从而恢复其活性并发挥抗肿瘤作用。临床研究表明,塞利尼索单药治疗或联合治疗在AML中均显示出良好的抗白血病效果,尤其是在复发/难治性AML患者中。此外,塞利尼索与其他药物如去甲基化药物和FLT3抑制剂联合使用已显示出协同抗肿瘤作用。尽管塞利尼索已显示出潜力,但其耐药性和不良反应仍需进一步研究和控制。未来的研究方向包括探索最佳用药方案、明确合适的人群以及制定新的联合治疗方案,以提高治疗效果并克服耐药问题。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fed9/12129985/ebba16d24475/fphar-16-1602911-g001.jpg

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