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

Autor: Sokolova V; Department of Nuclear Medicine, Provincial Hospital of Bolzano (SABES-ASDAA), Teaching Hospital of the Paracelsus Medical Private University, Bolzano-Bozen, Italy., Gruber R; Department of Hematology and Oncology, Comprehensive Cancer Center Innsbruck, Medical University of Innsbruck, Innsbruck, Austria., Pammer LM; Department of Medicine I, Gastroenterology, Hepatology and Endocrinology, Medical University of Innsbruck, Innsbruck, Austria., Kocher F; Department of Hematology and Oncology, Comprehensive Cancer Center Innsbruck, Medical University of Innsbruck, Innsbruck, Austria., Klieser E; Institute of Pathology, University Clinics Salzburg, Paracelsus Medical University, Salzburg, Austria.; Cancer Cluster Salzburg, Salzburg, Austria., Amann A; Department of Hematology and Oncology, Comprehensive Cancer Center Innsbruck, Medical University of Innsbruck, Innsbruck, Austria., Pichler R; Department of Urology, Medical University of Innsbruck, Innsbruck, Austria., Günther M; Institute of Pathology, INNPATH GmbH, Tirol Kliniken Innsbruck, Innsbruck, Austria., Ormanns S; Institute of Pathology, INNPATH GmbH, Tirol Kliniken Innsbruck, Innsbruck, Austria., Neureiter D; Institute of Pathology, University Clinics Salzburg, Paracelsus Medical University, Salzburg, Austria.; Cancer Cluster Salzburg, Salzburg, Austria., Seeber A; Department of Nuclear Medicine, Provincial Hospital of Bolzano (SABES-ASDAA), Teaching Hospital of the Paracelsus Medical Private University, Bolzano-Bozen, Italy. andreas.seeber@tirol-kliniken.at.; Department of Hematology and Oncology, Comprehensive Cancer Center Innsbruck, Medical University of Innsbruck, Innsbruck, Austria. andreas.seeber@tirol-kliniken.at.
Jazyk: angličtina
Zdroj: Molecular biology reports [Mol Biol Rep] 2024 Dec 27; Vol. 52 (1), pp. 87. Date of Electronic Publication: 2024 Dec 27.
DOI: 10.1007/s11033-024-10169-5
Abstrakt: 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.
Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval: Not applicable. Consent to participate: Not applicable. Consent to publish: Not applicable.
(© 2024. The Author(s).)
Databáze: MEDLINE
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