Selinexor和其他选择性核输出抑制剂-靶向血液恶性肿瘤和实体瘤的新方法

Kajetan Karaszewski, W. Jędrzejczak
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引用次数: 0

摘要

输出蛋白1 (XPO1)是核细胞质转运的重要分子。其中,它从细胞核向细胞质输出对肿瘤发生至关重要的分子。在许多恶性肿瘤中,XPO1的表达增加,从而导致肿瘤抑制蛋白在细胞质中的异常定位和随后的细胞周期失调。选择性核输出抑制剂(Selective inhibitors of nuclear export, SINEs)是一种新型的抗癌药物,它以XPO1为靶点,在细胞核中抑制肿瘤抑制蛋白,并诱导癌细胞凋亡。Selinexor是一种领先的SINE,已经被批准用于治疗复发/难治性多发性骨髓瘤和复发/难治性弥漫性大B细胞淋巴瘤。它也被证明对复发/难治性和以前未治疗的急性髓性白血病患者有效。此外,许多研究在其他造血系统恶性肿瘤和实体瘤中也取得了令人鼓舞的结果。然而,塞利纳索和其他SINEs的未来临床应用可能因其显著的毒性而受到阻碍。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Selinexor and Other Selective Inhibitors of Nuclear Export (SINEs)—A Novel Approach to Target Hematologic Malignancies and Solid Tumors
Exportin 1 (XPO1) is a crucial molecule of nucleocytoplasmic transport. Among others, it exports molecules important for oncogenesis from the nucleus to the cytoplasm. The expression of XPO1 is increased in numerous malignancies, which contributes to the abnormal localization of tumor suppressor proteins in the cytoplasm and subsequent cell cycle dysregulation. Selective inhibitors of nuclear export (SINEs) are novel anticancer agents that target XPO1, arrest tumor suppressor proteins in the nucleus, and induce apoptosis in cancer cells. Selinexor, a first-in-class SINE, has already been approved for the treatment of relapsed/refractory multiple myeloma and relapsed/refractory diffuse large B cell lymphoma not otherwise specified. It has also been proven effective in relapsed/refractory and previously untreated acute myeloid leukemia patients. In addition, numerous studies have yielded promising results in other malignancies of the hematopoietic system and solid tumors. However, future clinical use of selinexor and other SINEs may be hampered by their significant toxicity.
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