An evaluation of selinexor as a maintenance therapy for patients with p53 wild-type, advanced, or recurrent endometrial carcinoma.

IF 2.8 3区医学 Q2 ONCOLOGY

Expert Review of Anticancer Therapy Pub Date : 2025-09-01 Epub Date: 2025-06-29 DOI:10.1080/14737140.2025.2522948

Robert L Coleman, Pratheek Kalyanapu, Christopher J Walker, Ignace Vergote

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引用次数: 0

Abstract

Introduction: Tumor protein 53 gene (TP53) is the most frequently mutated gene in human cancers. TP53 mutation status may have prognostic value across malignancy types, and its use as a predictive biomarker is limited. Selinexor is a novel oral exportin 1 (XPO1) inhibitor with preliminary efficacy data as a maintenance treatment in advanced/recurrent TP53 wild-type (wt) endometrial cancer (EC), suggesting TP53wt may be a predictive biomarker for this therapy. XPO1 mediates nuclear to cytoplasmic trafficking of transcriptionally active p53, where it is degraded and rendered functionally inactive. Selinexor prevents this export to restore nuclear p53 and increase the transcription of p53 activated target genes.

Areas covered: This review examines the mechanism of action of selinexor related to p53, contextualizes the effectiveness of selinexor among EC subtypes within the context of the evolving diagnostic, predictive, and therapeutic landscape for treatment, and presents the relevant clinical studies for selinexor dose for its use in gynecological malignancies. Literature review was conducted on the PubMed database.

Expert opinion: The promising efficacy signal suggests selinexor has potential as a maintenance therapy for TP53wt EC to address current treatment gaps. A phase 3 study is currently enrolling to further evaluate its role in patients with advanced/recurrent EC.

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selinexor作为p53野生型、晚期或复发性子宫内膜癌患者维持治疗的评价

肿瘤蛋白53基因（Tumor protein 53 gene, TP53）是人类肿瘤中最常见的突变基因。TP53突变状态可能在各种恶性肿瘤类型中具有预后价值，但其作为预测性生物标志物的用途有限。Selinexor是一种新型口服输出蛋白1 （XPO1）抑制剂，作为晚期/复发性TP53野生型（wt）子宫内膜癌（EC）的维持治疗，初步疗效数据表明TP53wt可能是该治疗的预测性生物标志物。XPO1介导转录活性p53的核到细胞质运输，在那里它被降解并使功能失活。Selinexor阻止这种输出以恢复核p53并增加p53激活靶基因的转录。涵盖领域：本综述探讨了selinexor与p53相关的作用机制，在不断发展的诊断、预测和治疗前景的背景下，介绍了selinexor在EC亚型中的有效性，并介绍了selinexor剂量用于妇科恶性肿瘤的相关临床研究。在PubMed数据库中进行文献综述。专家意见：有希望的疗效信号表明，selinexor有潜力作为TP53wt EC的维持治疗，以弥补目前的治疗空白。目前正在进行一项3期研究，以进一步评估其在晚期/复发性EC患者中的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Expert Review of Anticancer Therapy 医学-肿瘤学

CiteScore

5.10

自引率

3.00%

发文量

100

审稿时长

4-8 weeks

期刊介绍： Expert Review of Anticancer Therapy (ISSN 1473-7140) provides expert appraisal and commentary on the major trends in cancer care and highlights the performance of new therapeutic and diagnostic approaches. Coverage includes tumor management, novel medicines, anticancer agents and chemotherapy, biological therapy, cancer vaccines, therapeutic indications, biomarkers and diagnostics, and treatment guidelines. All articles are subject to rigorous peer-review, and the journal makes an essential contribution to decision-making in cancer care. Comprehensive coverage in each review is complemented by the unique Expert Review format and includes the following sections: Expert Opinion - a personal view of the data presented in the article, a discussion on the developments that are likely to be important in the future, and the avenues of research likely to become exciting as further studies yield more detailed results Article Highlights – an executive summary of the author’s most critical points.