Dependency of EGFR activation in vanadium-based sensitization to oncolytic virotherapy
Oncolytic virotherapy is a clinically validated approach to treat cancers such as melanoma; however, tumor resistance to virus makes its efficacy variable. Compounds such as sodium orthovanadate (vanadate) can overcome viral resistance and synergize with RNA-based oncolytic viruses. In this study, w...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-06-01
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| Series: | Molecular Therapy: Oncolytics |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2372770522000560 |
| _version_ | 1811307000261246976 |
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| author | Boaz Wong Anabel Bergeron Nouf Alluqmani Glib Maznyi Andrew Chen Rozanne Arulanandam Jean-Simon Diallo |
| author_facet | Boaz Wong Anabel Bergeron Nouf Alluqmani Glib Maznyi Andrew Chen Rozanne Arulanandam Jean-Simon Diallo |
| author_sort | Boaz Wong |
| collection | DOAJ |
| description | Oncolytic virotherapy is a clinically validated approach to treat cancers such as melanoma; however, tumor resistance to virus makes its efficacy variable. Compounds such as sodium orthovanadate (vanadate) can overcome viral resistance and synergize with RNA-based oncolytic viruses. In this study, we explored the basis of vanadate mode of action and identified key cellular components in vanadate’s oncolytic virus-enhancing mechanism using a high-throughput kinase inhibitor screen. We found that several kinase inhibitors affecting signaling downstream of the epidermal growth factor receptor (EGFR) pathway abrogated the oncolytic virus-enhancing effects of vanadate. EGFR pathway inhibitors such as gefitinib negated vanadate-associated changes in the phosphorylation and localization of STAT1/2 as well as NF-κB signaling. Moreover, gefitinib treatment could abrogate the viral sensitizing response of vanadium compounds in vivo. Together, we demonstrate that EGFR signaling plays an integral role in vanadium viral sensitization and that pharmacological EGFR blockade can counteract vanadium/oncolytic virus combination therapy. |
| first_indexed | 2024-04-13T08:56:51Z |
| format | Article |
| id | doaj.art-b7838df85c4c411d8344541b202410f0 |
| institution | Directory Open Access Journal |
| issn | 2372-7705 |
| language | English |
| last_indexed | 2024-04-13T08:56:51Z |
| publishDate | 2022-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Oncolytics |
| spelling | doaj.art-b7838df85c4c411d8344541b202410f02022-12-22T02:53:16ZengElsevierMolecular Therapy: Oncolytics2372-77052022-06-0125146159Dependency of EGFR activation in vanadium-based sensitization to oncolytic virotherapyBoaz Wong0Anabel Bergeron1Nouf Alluqmani2Glib Maznyi3Andrew Chen4Rozanne Arulanandam5Jean-Simon Diallo6Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON K1H 8L6 Canada; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, CanadaCentre for Innovative Cancer Research, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON K1H 8L6 Canada; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, CanadaCentre for Innovative Cancer Research, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON K1H 8L6 Canada; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, CanadaCentre for Innovative Cancer Research, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON K1H 8L6 CanadaCentre for Innovative Cancer Research, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON K1H 8L6 CanadaCentre for Innovative Cancer Research, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON K1H 8L6 CanadaCentre for Innovative Cancer Research, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON K1H 8L6 Canada; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada; Corresponding author Jean-Simon Diallo, PhD, Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON K1H 8L6 Canada.Oncolytic virotherapy is a clinically validated approach to treat cancers such as melanoma; however, tumor resistance to virus makes its efficacy variable. Compounds such as sodium orthovanadate (vanadate) can overcome viral resistance and synergize with RNA-based oncolytic viruses. In this study, we explored the basis of vanadate mode of action and identified key cellular components in vanadate’s oncolytic virus-enhancing mechanism using a high-throughput kinase inhibitor screen. We found that several kinase inhibitors affecting signaling downstream of the epidermal growth factor receptor (EGFR) pathway abrogated the oncolytic virus-enhancing effects of vanadate. EGFR pathway inhibitors such as gefitinib negated vanadate-associated changes in the phosphorylation and localization of STAT1/2 as well as NF-κB signaling. Moreover, gefitinib treatment could abrogate the viral sensitizing response of vanadium compounds in vivo. Together, we demonstrate that EGFR signaling plays an integral role in vanadium viral sensitization and that pharmacological EGFR blockade can counteract vanadium/oncolytic virus combination therapy.http://www.sciencedirect.com/science/article/pii/S2372770522000560EGFRoncolytic virotherapyvanadiuminterferoncell signalingviral sensitization |
| spellingShingle | Boaz Wong Anabel Bergeron Nouf Alluqmani Glib Maznyi Andrew Chen Rozanne Arulanandam Jean-Simon Diallo Dependency of EGFR activation in vanadium-based sensitization to oncolytic virotherapy Molecular Therapy: Oncolytics EGFR oncolytic virotherapy vanadium interferon cell signaling viral sensitization |
| title | Dependency of EGFR activation in vanadium-based sensitization to oncolytic virotherapy |
| title_full | Dependency of EGFR activation in vanadium-based sensitization to oncolytic virotherapy |
| title_fullStr | Dependency of EGFR activation in vanadium-based sensitization to oncolytic virotherapy |
| title_full_unstemmed | Dependency of EGFR activation in vanadium-based sensitization to oncolytic virotherapy |
| title_short | Dependency of EGFR activation in vanadium-based sensitization to oncolytic virotherapy |
| title_sort | dependency of egfr activation in vanadium based sensitization to oncolytic virotherapy |
| topic | EGFR oncolytic virotherapy vanadium interferon cell signaling viral sensitization |
| url | http://www.sciencedirect.com/science/article/pii/S2372770522000560 |
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