Coleman Robert L, Kalyanapu Pratheek, Walker Christopher J, Vergote Ignace
Gynecologic Oncology Group (GOG)-Foundation and Texas Oncology, Georgetown, TX, USA.
Karyopharm Therapeutics, Newton, MA, USA.
Expert Rev Anticancer Ther. 2025 Jun 29:1-13. doi: 10.1080/14737140.2025.2522948.
Tumor protein 53 gene () is the most frequently mutated gene in human cancers. 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 wild-type (wt) endometrial cancer (EC), suggesting wt 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.
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.
The promising efficacy signal suggests selinexor has potential as a maintenance therapy for wt EC to address current treatment gaps. A phase 3 study is currently enrolling to further evaluate its role in patients with advanced/recurrent EC.
肿瘤蛋白53基因（）是人类癌症中最常发生突变的基因。突变状态可能在多种恶性肿瘤类型中具有预后价值，但其作为预测生物标志物的应用有限。塞利尼索是一种新型口服核输出蛋白1（XPO1）抑制剂，在晚期/复发性野生型（wt）子宫内膜癌（EC）的维持治疗中具有初步疗效数据，提示wt可能是该疗法的预测生物标志物。XPO1介导转录活性p53从细胞核向细胞质的转运，在细胞质中p53被降解并失去功能活性。塞利尼索可阻止这种输出，从而恢复细胞核内的p53并增加p53激活的靶基因的转录。
本综述探讨了塞利尼索与p53相关的作用机制，在不断发展的EC诊断、预测和治疗格局背景下，将塞利尼索在EC亚型中的有效性进行了背景化分析，并介绍了塞利尼索用于妇科恶性肿瘤的相关临床研究剂量。在PubMed数据库上进行了文献综述。
有前景的疗效信号表明，塞利尼索有潜力作为wt EC的维持疗法，以填补当前的治疗空白。目前一项3期研究正在招募患者，以进一步评估其在晚期/复发性EC患者中的作用。
