Nuclear Export Inhibitor Selinexor Enhances Oncolytic Myxoma Virus Therapy against Cancer

Rahman, Masmudur M.; Oosterom, Fleur van; Enow, Junior Ayuk; Hossain, Maksuda; Gutierrez-Jensen, Ami D; Cashen, Mackenzie; Everts, Anne; Lowe, Kenneth; Kilbourne, Jacquelyn; Daggett-Vondras, Juliane; Karr, Timothy L.; McFadden, Grant

doi:10.1158/2767-9764.crc-22-0483

Cited by 4 publications

(1 citation statement)

References 60 publications

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“…MDM2 is a negative regulator of the tumour suppressor protein p53, while XPO1 participates in the nuclear export of various proteins. HUWE1 and NEDD8 are implicated in processes related to protein stabilization, degradation and ubiquitination 47–50 …”

Section: Resultsmentioning

confidence: 99%

Comprehensive modular analyses of scar subtypes illuminate underlying molecular mechanisms and potential therapeutic targets

Liu,

Lu,

Qiu

et al. 2023

International Wound Journal

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Pathological scarring resulting from traumas and wounds, such as hypertrophic scars and keloids, pose significant aesthetic, functional and psychological challenges. This study provides a comprehensive transcriptomic analysis of these conditions, aiming to illuminate underlying molecular mechanisms and potential therapeutic targets. We employed a co‐expression and module analysis tool to identify significant gene clusters associated with distinct pathophysiological processes and mechanisms, notably lipid metabolism, sebum production, cellular energy metabolism and skin barrier function. This examination yielded critical insights into several skin conditions including folliculitis, skin fibrosis, fibrosarcoma and congenital ichthyosis. Particular attention was paid to Module Cluster (MCluster) 3, encompassing genes like BLK, TRPV1 and GABRD, all displaying high expression and potential implications in immune modulation. Preliminary immunohistochemistry validation supported these findings, showing elevated expression of these genes in non‐fibrotic samples rich in immune activity. The complex interplay of different cell types in scar formation, such as fibroblasts, myofibroblasts, keratinocytes and mast cells, was also explored, revealing promising therapeutic strategies. This study underscores the promise of targeted gene therapy for pathological scars, paving the way for more personalised therapeutic approaches. The results necessitate further research to fully ascertain the roles of these identified genes and pathways in skin disease pathogenesis and potential therapeutics. Nonetheless, our work forms a strong foundation for a new era of personalised medicine for patients suffering from pathological scarring.

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Section: Resultsmentioning

confidence: 99%

Comprehensive modular analyses of scar subtypes illuminate underlying molecular mechanisms and potential therapeutic targets

Liu,

Lu,

Qiu

et al. 2023

International Wound Journal

View full text Add to dashboard Cite

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Targeting XPO1 for fighting relapsed/refractory diseases: The research progress of XPO1 inhibitors

Li,

Fang,

Zhang

et al. 2025

Bioorganic Chemistry

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Effect of exportin 1/XPO1 nuclear export pathway inhibition on coronavirus replication

Rahman

Estifanos

Glenn

et al. 2023

Preprint

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Nucleocytoplasmic transport of proteins using XPO1 (exportin 1) plays a vital role in cell proliferation and survival. Many viruses also exploit this pathway to promote infection and replication. Thus, inhibiting XPO1-mediated nuclear export with selective inhibitors activates multiple antiviral and anti-inflammatory pathways. The XPO1 inhibitor, Selinexor, is an FDA-approved anticancer drug predicted to have antiviral function against many viruses, including SARS-CoV-2. Unexpectedly, we observed that pretreatment of cultured human cells with Selinexor actually enhanced protein expression and replication of coronaviruses, including SARS-CoV-2. Knockdown of cellular XPO1 protein expression significantly enhanced the replication of coronaviruses in human cells. We further demonstrate that Selinexor treatment reduced the formation of unique cytoplasmic antiviral granules that include RNA helicase DHX9 in the virus-infected cells. These results, for the first time, show that the anti-cancer drug Selinexor enhances the replication of coronaviruses in human cells in vitro and thus should be further explored in vivo for the potential impact on the dual use for anticancer and antiviral therapy.

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Nuclear Export Inhibitor Selinexor Enhances Oncolytic Myxoma Virus Therapy against Cancer

Cited by 4 publications

References 60 publications

Comprehensive modular analyses of scar subtypes illuminate underlying molecular mechanisms and potential therapeutic targets

Comprehensive modular analyses of scar subtypes illuminate underlying molecular mechanisms and potential therapeutic targets

Targeting XPO1 for fighting relapsed/refractory diseases: The research progress of XPO1 inhibitors

Effect of exportin 1/XPO1 nuclear export pathway inhibition on coronavirus replication

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