Prognostic and functional role of the nuclear export receptor 1 (XPO1) in gastrointestinal cancers - a potential novel target?

Sep 21, 2026

Uploaded by Theodora

Survival of metastatic gastrointestinal (GI) cancer patients has improved through targeted and immunotherapy, yet most patients still do not achieve durable benefit, making new therapeutic options necessary. Molecular high-throughput profiling highlights actionable alterations, and nuclear export proteins have gained attention as targets because they regulate key cellular functions and homeostasis. Dysregulated XPO1-driven nuclear export can inactivate tumor suppressors and pro-apoptotic factors, supporting cancer progression. Selinexor, an XPO1 inhibitor, shows promise in hematologic malignancies, while its GI efficacy remains insufficiently characterized. This review synthesizes XPO1’s functional and pathophysiological role and argues for further validation of selective inhibitors guided by GI tumor expression profiles.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages30

Reading Time1 h 16 min

AccessFree to download

Abstract

Background and need for novel GI cancer therapeutics

XPO1 biology and rationale for targeting nuclear export

Evidence for selinexor and knowledge gaps in GI cancers

Aim and expected impact of targeting XPO1

Introduction

Personalized cancer therapy and molecular profiling

Targeting nuclear export proteins as a therapeutic strategy

Molecular Biology Reports (2025) 52:87 [https://doi.org/10.1007/s1](https://doi.org/10.1007/s1) 1033-024-10169-5 Prognostic and functional role of the nuclear export receptor 1 (XPO1) in gastrointestinal cancers: a potential novel target? Viktorija Sokolova1 · Rebecca Gruber2 · Lorenz M. Pammer3 · Florian Kocher2 · Eckhard Klieser4,5 · Arno Amann2 · Renate Pichler6 · Michael Günther7 · Steffen Ormanns7 · Daniel Neureiter4,5 · Andreas Seeber1,2 Received: 18 June 2024 / Accepted: 10 December 2024 / Published online: 27 December 2024 © The Author(s) 2024 Abstract In the last decades the survival of metastatic gastrointestinal (GI) cancer patients could have been significantly extended due to the introduction of targeted-and immunotherapy. However, only the minority of patients will experience long-lasting survival. Hence, novel therapeutics are clearly necessary for GI cancer patients. Molecular high-throughput profiling techniques have revealed potential novel targetable molecular alterations, emphasizing the necessity for tailored therapeutic approaches. Nuclear export proteins, particularly Exportin-1 (XPO1), have emerged as promising targets in cancer therapy due to their crucial role in cellular homeostasis and regulation of key cellular functions. Dysregulation of XPO1-mediated nuclear export leads to the functional loss of tumor suppressors and pro-apoptotic factors, facilitating cancer progression. Selinexor, a XPO1 inhibitor, has shown promising activity in preclinical and clinical studies, particularly in hematological malignancies. However, its efficacy in GI cancers remains underexplored. This review aims to elucidate the functional and pathophysiological role of XPO1 in GI cancers. Despite the potential of XPO1 inhibitors in suppressing cell proliferation and inducing apoptosis, comprehensive molecular landscape data and validation of selective inhibitors in GI cancers are lacking. Targeting XPO1 presents a significant therapeutic potential for the treatment of GI cancer patients. Further research is necessary to fully elucidate the molecular landscape according to XPO1 expression in GI tumors and to validate the efficacy of selective XPO1 inhibitors. These efforts are expected to contribute to the development of more effective and personalized therapeutic strategies for GI cancer patients. Keywords SINE · Selinexor · Gastrointestinal cancers · XPO1 · Cancer therapy · Nuclear export proteins · XPO1 inhibitor Abbreviations ATR Ataxia telangiectasia mutated-Rad3-related BCR B-cell receptor BTK Bruton tyrosine kinase Viktorija Sokolova, Rebecca Gruber, Lorenz M. Pammer, Daniel Neureiter, and Andreas Seeber have contributed equally. * Andreas Seeber [andreas.seeber@tirol-kliniken.at](andreas.seeber@tirol-kliniken.at) 1 Department of Nuclear Medicine, Provincial Hospital of Bolzano (SABES-ASDAA), Teaching Hospital of the Paracelsus Medical Private University, Bolzano-Bozen, Italy 2 Department of Hematology and Oncology, Comprehensive Cancer Center Innsbruck, Medical University of Innsbruck, Innsbruck, Austria 3 Department of Medicine I, Gastroenterology, Hepatology and Endocrinology, Medical University of Innsbruck, Innsbruck, Austria CC Cholangiocarcinoma cHL Classical Hodgkin's lymphoma CLL Lymphocytic leukemia CRC Colorectal cancer CRM1 Chromosome region maintenance 1 CSC Cancer stem cells 4 Institute of Pathology, University Clinics Salzburg, Paracelsus Medical University, Salzburg, Austria 5 Cancer Cluster Salzburg, Salzburg, Austria 6 Department of Urology, Medical University of Innsbruck, Innsbruck, Austria 7 Institute of Pathology, INNPATH GmbH, Tirol Kliniken Innsbruck, Innsbruck, Austria DCR DDK DDR DLBCL EC EGFR ESCC GBC GC GI GIT GIST HCC IAP MM miRNAs NES NEN NLS NPC OS PAR-4 PDAC PFS PMBL Ran RanGAP RCC1 SINE SI-NETs TET TSPs XPO1 Disease control rates DBF4-dependent kinase DNA damage respons

FAQs

Why are new therapeutics needed for gastrointestinal cancers?

Most metastatic GI cancer patients do not achieve long-lasting survival despite targeted and immunotherapy advances, so new therapeutic strategies are required.

What is the functional significance of XPO1 in cancer progression?

XPO1-mediated nuclear export dysregulation can cause functional loss of tumor suppressors and pro-apoptotic factors, facilitating cancer progression.

How does selinexor relate to XPO1 and what is known about its effectiveness in GI cancers?

Selinexor is an XPO1 inhibitor with promising preclinical and clinical activity in hematological malignancies, but its efficacy in GI cancers is still underexplored.

Sep 21, 2026

Uploaded by Theodora