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塞利尼索,核输出抑制剂:血液癌症的非选择性子弹。

Selinexor, selective inhibitor of nuclear export: Unselective bullet for blood cancers.

机构信息

Department of Hematooncology, University Hospital Ostrava, 17. listopadu 1790/5, Ostrava 708 52, Czech Republic; Faculty of Medicine, University of Ostrava, Ostrava 703 00, Czech Republic.

出版信息

Blood Rev. 2021 Mar;46:100758. doi: 10.1016/j.blre.2020.100758. Epub 2020 Sep 15.

Abstract

Exportin 1 (XPO1), also known as chromosome maintenance 1 protein (CRM1), is the main transporter for hundreds of proteins like tumor suppressors, growth regulatory factors, oncoprotein mRNAs and others. Its upregulation leads to the inactivation of the tumor suppressor anti-neoplastic function in many cancers and logically is associated with poor prognosis. Selective inhibitors of nuclear export (SINE) are a new generation of XPO1 inhibitors that are being investigated as a promising targeted anti-cancer therapy. Selinexor is the first generation of SINE compounds that is being evaluated in many clinical trials involving solid tumors and hematological malignancies with its two approved indications for relapsed multiple myeloma and relapsed diffuse large B-cell lymphoma. Here, we comprehensively review the current knowledge of selinexor and next generations of the SINE compounds in lymphoid and myeloid malignancies.

摘要

Exportin 1(XPO1),也称为染色体维持 1 蛋白(CRM1),是数百种蛋白质(如肿瘤抑制因子、生长调节因子、癌蛋白 mRNA 等)的主要转运蛋白。其上调导致许多癌症中肿瘤抑制因子抗肿瘤功能失活,逻辑上与预后不良相关。核输出的选择性抑制剂(SINE)是新一代 XPO1 抑制剂,正在作为一种有前途的靶向抗癌疗法进行研究。Selinexor 是第一代 SINE 化合物,正在许多涉及实体瘤和血液恶性肿瘤的临床试验中进行评估,其两种已批准的适应症为复发多发性骨髓瘤和复发弥漫性大 B 细胞淋巴瘤。在这里,我们全面回顾了 selinexor 及其在淋巴和髓系恶性肿瘤中的新一代 SINE 化合物的现有知识。

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