PUBLICATION
An evaluation of selinexor as a maintenance therapy for patients with p53 wild-type, advanced, or recurrent endometrial carcinoma
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.
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.
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
therapy for TP53wt EC to address current treatment gaps. A phase
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