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High XPO1 levels correlate with worse outcomes because oncogenic cargo export supports tumor progression and treatment resistance. The review summarizes identified XPO1 protein and RNA cargos in NHL, then discusses preclinical and clinical evidence for XPO1 inhibitors, including selinexor and selective nuclear export (SINE) agents, and considers current limitations and future research directions.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/nuclear-export-in-non-hodgkin-lymphoma-and-implications-for-targeted-xpo1-inhibitors/406596/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/nuclear-export-in-non-hodgkin-lymphoma-and-implications-for-targeted-xpo1-inhibitors/406596.png","ImageObject",300,407,{"name":92,"@type":93},"jayni","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-05","2026-09-28",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why is XPO1 important in non-Hodgkin lymphoma (NHL)?","Question",{"text":112,"@type":113},"XPO1 is a central component of nuclear export and is overexpressed in cancers. In NHL, high XPO1 expression is linked to poor prognosis because it exports proteins and RNA that promote tumor progression and treatment resistance.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What types of cargo does XPO1 transport in NHL?",{"text":117,"@type":113},"The review highlights proteins and RNA transcripts identified as XPO1 cargo in NHL, including tumor suppressors, immune modulators, and transcription factors that influence oncogenesis.",{"name":119,"@type":110,"acceptedAnswer":120},"Which XPO1 inhibitors are discussed for treating NHL?",{"text":121,"@type":113},"The review focuses on XPO1-targeted agents such as selinexor and other selective nuclear export inhibitors (SINEs). It reports anti-cancer effects supported by in vitro, in vivo, and clinical studies, including use as monotherapy and in combination.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},406596,1790811767,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":39,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},3985747859343,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","biomolecules  \nReview  \nNuclear Export in Non-Hodgkin Lymphoma and Implications for Targeted XPO1 Inhibitors  \nKyla L. Trkulja 1,2, Farheen Manji 2, John Kuruvilla 1,2 and Rob C. Laister 2, *  \nCitation: Trkulja, K.L.; Manji, F.; Kuruvilla, J.; Laister, R.C. Nuclear Export in Non-Hodgkin Lymphoma and Implications for Targeted XPO1 Inhibitors. Biomolecules 2023, 13, 111 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)biom13010111  \nAcademic Editors: Thomas E. Witzig, Jithma P. Abeykoon, Saurabh Zanwar and Xavier Andrade-Gonzalez  \nReceived: 1 December 2022  \nRevised: 21 December 2022  \nAccepted: 24 December 2022  \nPublished: 5 January 2023  \nCopyright: © 2023 by the authors. 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://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Institute of Medical Science, University of Toronto, 27 King's College Circle, Toronto, ON M5S 1A1, Canada  \n2 Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, 610 University Avenue, Toronto, ON M5G 2C1, Canada  \n* Correspondence: [rob.laister@uhnresearch.ca](rob.laister@uhnresearch.ca)  \nAbstract: 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 foroncogenesis. 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.  \nKeywords: lymphoma; hematology; cancer; nuclear export; targeted therapy; proteomics  \n1. Introduction  \nMammalian cells are segregated and organized into different compartments in part through the use of lipid membranes. The deployment of membranes in this manner creates functional hubs that separates processes such as energy production (mitochondria), from proteins/fat synthesis and calcium storage (endoplasmic reticulum) and containment of genetic material (nucleus) . The correct spatiotemporal localization of molecules is controlled by a variety of mechanisms and a failure to compartmentalize molecules in time and space can lead to diseased states. The nuclear compartment is separated from the cytosol by the nuclear envelope and transport between these two locales is regulated by the nuclear pore complex (NPC) . The NPC is a semi-selective barrier that allows the free passage of molecules between 40 and 60 kDa and requires active transport mechanisms for molecules exceeding this molecular weight limit [1] . Given the distinct roles of these compartments, managing transport between the cytoplasm and the nucleus is critical for maintaining cellular homeostasis. The NPC ensures that elements essential for maintaining genomic fidelity remain in the nucleus as required. In the case of possible underlying mechanisms of lymphomagenesis, it is essential that the DNA repair machinery be localized in the nuclear compartment to detect and repair genetic lesions that coul","cbCaimNDVk70kFxu","https://ap.wps.com/l/cbCaimNDVk70kFxu","pdf",328948,17,"English","# Introduction\n## Nuclear compartmentalization and nuclear-cytoplasmic transport\n## Nuclear export, p53 mislocalization, and lymphoma biology\n## Karyopherins and XPO1 as a therapeutic target\n# Abstract Overview\n## XPO1 cargo in NHL\n## XPO1 inhibitors and evidence from studies\n## Limitations and future directions","[{\"question\":\"Why is XPO1 important in non-Hodgkin lymphoma (NHL)?\",\"answer\":\"XPO1 is a central component of nuclear export and is overexpressed in cancers. In NHL, high XPO1 expression is linked to poor prognosis because it exports proteins and RNA that promote tumor progression and treatment resistance.\"},{\"question\":\"What types of cargo does XPO1 transport in NHL?\",\"answer\":\"The review highlights proteins and RNA transcripts identified as XPO1 cargo in NHL, including tumor suppressors, immune modulators, and transcription factors that influence oncogenesis.\"},{\"question\":\"Which XPO1 inhibitors are discussed for treating NHL?\",\"answer\":\"The review focuses on XPO1-targeted agents such as selinexor and other selective nuclear export inhibitors (SINEs). It reports anti-cancer effects supported by in vitro, in vivo, and clinical studies, including use as monotherapy and in combination.\"}]","Nuclear Export in Non-Hodgkin Lymphoma and Implications for Targeted XPO1 Inhibitors | PDF",1790566617,43]