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

被引：1

作者：

Sokolova, Viktorija ^{[1
]}

Gruber, Rebecca ^{[2
]}

Pammer, Lorenz M. ^{[3
]}

Kocher, Florian ^{[2
]}

Klieser, Eckhard ^{[4
,5
]}

Amann, Arno ^{[2
]}

Pichler, Renate ^{[6
]}

Guenther, Michael ^{[7
]}

Ormanns, Steffen ^{[7
]}

Neureiter, Daniel ^{[4
,5
]}

Seeber, Andreas ^{[1
,2
]}

机构：

[1] Paracelsus Med Private Univ, Teaching Hosp, Prov Hosp Bolzano SABES ASDAA, Dept Nucl Med, Bolzano, Italy

[2] Med Univ Innsbruck, Comprehens Canc Ctr Innsbruck, Dept Hematol & Oncol, Innsbruck, Austria

[3] Med Univ Innsbruck, Dept Med 1, Gastroenterol Hepatol & Endocrinol, Innsbruck, Austria

[4] Univ Clin Salzburg, Paracelsus Med Univ, Inst Pathol, Salzburg, Austria

[5] Canc Cluster Salzburg, Salzburg, Austria

[6] Med Univ Innsbruck, Dept Urol, Innsbruck, Austria

[7] INNPATH GmbH, Tirol Kliniken Innsbruck, Inst Pathol, Innsbruck, Austria

来源：

MOLECULAR BIOLOGY REPORTS | 2025年 / 52卷 / 01期

关键词：

SINE; Selinexor; Gastrointestinal cancers; XPO1; Cancer therapy; Nuclear export proteins; inhibitor; ORDER CHROMOSOME STRUCTURE; TOPOISOMERASE-II-ALPHA; SELECTIVE INHIBITOR; DRUG-RESISTANCE; COLORECTAL-CANCER; STRUCTURAL BASIS; LEPTOMYCIN-B; OPEN-LABEL; RECURRENT MUTATIONS; ANTITUMOR-ACTIVITY;

D O I：

10.1007/s11033-024-10169-5

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页数：30