Dependency of EGFR activation in vanadium-based sensitization to oncolytic virotherapy.

Autor:	Wong B; Centre 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., Bergeron A; Centre 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., Alluqmani N; Centre 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., Maznyi G; Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON K1H 8L6 Canada., Chen A; Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON K1H 8L6 Canada., Arulanandam R; Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON K1H 8L6 Canada., Diallo JS; Centre 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.
Jazyk:	angličtina
Zdroj:	Molecular therapy oncolytics [Mol Ther Oncolytics] 2022 Apr 19; Vol. 25, pp. 146-159. Date of Electronic Publication: 2022 Apr 19 (Print Publication: 2022).
DOI:	10.1016/j.omto.2022.04.004
Abstrakt:	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. Competing Interests: J.S.D is co-inventor on a patent covering the use of vanadium compounds as enhancer of RNA viruses and holds shares in Virica Biotech and Virano Therapeutics that holds a license to this and related intellectual property. (© 2022 The Authors.)
Databáze:	MEDLINE
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