XPO1抑制剂在弥漫性大B细胞淋巴瘤中的研究进展

doi:10.11904/j.issn.1002-3070.2023.02.015

摘要/Abstract

摘要： 弥漫性大B细胞淋巴瘤(Diffuse large B-cell lymphoma,DLBCL)是一种常见的非霍奇金淋巴瘤,目前患者使用R-CHOP一线治疗方案的5年总生存率在60%~70%。DLBCL的异质性和侵袭性可能会导致一些患者在接受治疗后出现复发或进展为难治性疾病。作为核输出受体蛋白,核输出蛋白1(Exportin 1,XPO1)能够将超过220种蛋白及RNA从细胞核转运到细胞质,并优先转运癌蛋白及编码癌蛋白的mRNAs,可能参与肿瘤的发生发展。相关研究表明,XPO1在白血病和淋巴瘤等许多恶性肿瘤中过表达,并在DLBCL等B细胞恶性肿瘤中发生突变。XPO1抑制剂能够靶向抑制XPO1,阻断癌蛋白的核输出;也能限制XPO1与其靶蛋白如肿瘤抑制蛋白(Tumor suppressor protein,TSP)的结合,降低TSP的核输出,在恶性肿瘤中发挥抗癌活性。本文就XPO1抑制剂在DLBCL中的研究进展进行综述。

关键词: 核输出蛋白1, 弥漫性大B细胞淋巴瘤, Selinexor

Abstract: Diffuse large B-cell lymphoma(DLBCL)is a common form of non-Hodgkin′s lymphoma.Currently,the 5-year overall survival rate of patients treated with R-CHOP first-line therapy is 60% to 70%.The heterogeneous and aggressiveness of DLBCL may lead some patients to relapse or progress to refractory disease after receiving treatment.As a nuclear export receptor protein,exportin 1(XPO1)can transports more than 220 proteins and RNAs from the nucleus to the cytoplasm,and preferentially transport oncoproteins and mRNAs encoding oncoproteins,which may be involved in the occurrence and development of tumors.Related studies have shown that XPO1 is overexpressed in many malignant tumors such as leukemia and lymphoma,and mutates in B-cell malignancies such as DLBCL.XPO1 inhibitors can target XPO1 and block the nuclear output of oncoproteins;they can also limit the combination of XPO1 and its target proteins such as tumor suppressor protein(TSP),reduce the nuclear export of TSP,and play an anti-inflammatory role in malignant tumors.This article reviews the research progress of XPO1 inhibitors in DLBCL.

Key words: XPO1 inhibitor, Diffuse large B-cell lymphoma, Selinexor

中图分类号:

R733.4

李彤, 李博雅, 秦玲. XPO1抑制剂在弥漫性大B细胞淋巴瘤中的研究进展[J]. 实用肿瘤学杂志, 2023, 37(2): 175-180.

LI Tong, LI Boya, QIN Ling. Research progress of XPO1 inhibitors in diffuse large B-cell lymphoma[J]. Journal of Practical Oncology, 2023, 37(2): 175-180.

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