Exportin-1 (XPO1) 是一种调节核质运输的关键蛋白，在各种癌症中经常过度表达，从而驱动肿瘤进展和耐药性。这使得 XPO1 成为一个有吸引力的治疗靶点。在过去的几十年里，可用的核输出选择性抑制剂的数量一直在增加。只有KPT-330（selinexor）已成功用于治疗血液恶性肿瘤，KPT-8602（eltanexor）已在临床试验中用于治疗血液肿瘤。然而，核输出选择性抑制剂用于抑制XPO1表达的用途尚未在实体瘤的临床研究和治疗结果中得到彻底研究。我们收集了大量文献来解释XPO1抑制剂在临床前和临床研究中的功效。在这篇综述中，我们重点关注 XPO1 的核输出功能及其抑制剂在实体恶性肿瘤中的临床试验结果。我们总结了 XPO1 抑制剂的作用机制和治疗潜力，以及不良反应和反应生物标志物。XPO1 抑制已成为抗击癌症的一种有前景的治疗策略，为靶向致瘤过程和克服耐药性提供了一种新方法。 SINE 化合物已在多种实体瘤中表现出功效，正在进行的研究重点是优化其使用、识别反应生物标志物和开发有效的联合疗法。Exportin-1 (XPO1) 在介导核细胞质转运和细胞周期中发挥着关键作用。 XPO1 功能障碍会促进实体瘤内的肿瘤发生和耐药性。 XPO1 抑制剂治疗实体瘤的治疗潜力和正在进行的研究。额外的研究对于解决安全问题和确定预测患者对 XPO1 抑制剂反应的生物标志物至关重要。© 2024 作者。约翰·威利出版的《临床与转化医学》

Exportin-1 (XPO1), a crucial protein regulating nuclear-cytoplasmic transport, is frequently overexpressed in various cancers, driving tumor progression and drug resistance. This makes XPO1 an attractive therapeutic target. Over the past few decades, the number of available nuclear export-selective inhibitors has been increasing. Only KPT-330 (selinexor) has been successfully used for treating haematological malignancies, and KPT-8602 (eltanexor) has been used for treating haematologic tumours in clinical trials. However, the use of nuclear export-selective inhibitors for the inhibition of XPO1 expression has yet to be thoroughly investigated in clinical studies and therapeutic outcomes for solid tumours.We collected numerous literatures to explain the efficacy of XPO1 Inhibitors in preclinical and clinical studies of a wide range of solid tumours.In this review, we focus on the nuclear export function of XPO1 and results from clinical trials of its inhibitors in solid malignant tumours. We summarized the mechanism of action and therapeutic potential of XPO1 inhibitors, as well as adverse effects and response biomarkers.XPO1 inhibition has emerged as a promising therapeutic strategy in the fight against cancer, offering a novel approach to targeting tumorigenic processes and overcoming drug resistance. SINE compounds have demonstrated efficacy in a wide range of solid tumours, and ongoing research is focused on optimizing their use, identifying response biomarkers, and developing effective combination therapies.Exportin-1 (XPO1) plays a critical role in mediating nucleocytoplasmic transport and cell cycle. XPO1 dysfunction promotes tumourigenesis and drug resistance within solid tumours. The therapeutic potential and ongoing researches on XPO1 inhibitors in the treatment of solid tumours. Additional researches are essential to address safety concerns and identify biomarkers for predicting patient response to XPO1 inhibitors.© 2024 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.