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

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.