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Nuclear Export in Non-Hodgkin Lymphoma and Implications for Targeted XPO1 Inhibitors

Exportin-1 (XPO1) is a key player in the nuclear export pathway and is overexpressed in almost all cancers. This is especially relevant for non-Hodgkin lymphoma (NHL), where high XPO1 expression is associated with poor prognosis due to its oncogenic role in exporting proteins and RNA that are involv...

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Autores principales: Trkulja, Kyla L., Manji, Farheen, Kuruvilla, John, Laister, Rob C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9855521/
https://www.ncbi.nlm.nih.gov/pubmed/36671496
http://dx.doi.org/10.3390/biom13010111
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author Trkulja, Kyla L.
Manji, Farheen
Kuruvilla, John
Laister, Rob C.
author_facet Trkulja, Kyla L.
Manji, Farheen
Kuruvilla, John
Laister, Rob C.
author_sort Trkulja, Kyla L.
collection PubMed
description Exportin-1 (XPO1) is a key player in the nuclear export pathway and is overexpressed in almost all cancers. This is especially relevant for non-Hodgkin lymphoma (NHL), where high XPO1 expression is associated with poor prognosis due to its oncogenic role in exporting proteins and RNA that are involved in cancer progression and treatment resistance. Here, we discuss the proteins and RNA transcripts that have been identified as XPO1 cargo in NHL lymphoma including tumour suppressors, immune modulators, and transcription factors, and their implications for oncogenesis. We then highlight the research to date on XPO1 inhibitors such as selinexor and other selective inhibitors of nuclear export (SINEs), which are used to treat some cases of non-Hodgkin lymphoma. In vitro, in vivo, and clinical studies investigating the anti-cancer effects of SINEs from bench to bedside, both as a single agent and in combination, are also reported. Finally, we discuss the limitations of the current research landscape and future directions to better understand and improve the clinical utility of SINE compounds in NHL.
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spelling pubmed-98555212023-01-21 Nuclear Export in Non-Hodgkin Lymphoma and Implications for Targeted XPO1 Inhibitors Trkulja, Kyla L. Manji, Farheen Kuruvilla, John Laister, Rob C. Biomolecules Review Exportin-1 (XPO1) is a key player in the nuclear export pathway and is overexpressed in almost all cancers. This is especially relevant for non-Hodgkin lymphoma (NHL), where high XPO1 expression is associated with poor prognosis due to its oncogenic role in exporting proteins and RNA that are involved in cancer progression and treatment resistance. Here, we discuss the proteins and RNA transcripts that have been identified as XPO1 cargo in NHL lymphoma including tumour suppressors, immune modulators, and transcription factors, and their implications for oncogenesis. We then highlight the research to date on XPO1 inhibitors such as selinexor and other selective inhibitors of nuclear export (SINEs), which are used to treat some cases of non-Hodgkin lymphoma. In vitro, in vivo, and clinical studies investigating the anti-cancer effects of SINEs from bench to bedside, both as a single agent and in combination, are also reported. Finally, we discuss the limitations of the current research landscape and future directions to better understand and improve the clinical utility of SINE compounds in NHL. MDPI 2023-01-05 /pmc/articles/PMC9855521/ /pubmed/36671496 http://dx.doi.org/10.3390/biom13010111 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Trkulja, Kyla L.
Manji, Farheen
Kuruvilla, John
Laister, Rob C.
Nuclear Export in Non-Hodgkin Lymphoma and Implications for Targeted XPO1 Inhibitors
title Nuclear Export in Non-Hodgkin Lymphoma and Implications for Targeted XPO1 Inhibitors
title_full Nuclear Export in Non-Hodgkin Lymphoma and Implications for Targeted XPO1 Inhibitors
title_fullStr Nuclear Export in Non-Hodgkin Lymphoma and Implications for Targeted XPO1 Inhibitors
title_full_unstemmed Nuclear Export in Non-Hodgkin Lymphoma and Implications for Targeted XPO1 Inhibitors
title_short Nuclear Export in Non-Hodgkin Lymphoma and Implications for Targeted XPO1 Inhibitors
title_sort nuclear export in non-hodgkin lymphoma and implications for targeted xpo1 inhibitors
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9855521/
https://www.ncbi.nlm.nih.gov/pubmed/36671496
http://dx.doi.org/10.3390/biom13010111
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