Oncolytic vesicular stomatitis virus alone or in combination with JAK inhibitors is effective against ovarian cancer
Therapy-resistant ovarian cancers have a poor prognosis and novel effective treatment options are urgently needed. In this study, we evaluated the therapeutic efficacy of the oncolytic vesicular stomatitis virus (VSV) against a panel of patient-derived ovarian cancer cell lines of all epithelial sub...
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| Language: | English |
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Elsevier
2024-09-01
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| Series: | Molecular Therapy: Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2950329924000687 |
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| author | Karen Geoffroy Victor Mullins-Dansereau Kim Leclerc-Desaulniers Mélissa Viens Marie-Claude Bourgeois-Daigneault |
| author_facet | Karen Geoffroy Victor Mullins-Dansereau Kim Leclerc-Desaulniers Mélissa Viens Marie-Claude Bourgeois-Daigneault |
| author_sort | Karen Geoffroy |
| collection | DOAJ |
| description | Therapy-resistant ovarian cancers have a poor prognosis and novel effective treatment options are urgently needed. In this study, we evaluated the therapeutic efficacy of the oncolytic vesicular stomatitis virus (VSV) against a panel of patient-derived ovarian cancer cell lines of all epithelial subtypes. Notably, we found that most of the cell lines were sensitive to VSV virotherapy. With the objective of improving treatment efficacy for the oncolytic virus-resistant cell lines, we tested various combinations with ovarian cancer standard of care drugs: olaparib, carboplatin, paclitaxel, doxorubicin, cyclophosphamide, and gemcitabine. While none of these combinations revealed to be beneficial, further experiments demonstrated that the antiviral interferon pathway was functional in VSV-resistant cell lines. Given that interferons signal through Janus kinase (JAK)-STAT to mediate their antiviral function, we tested combinations of oncolytic VSV with clinically relevant JAK inhibitors. Our results show that combining VSV with various JAK inhibitors, including ruxolitinib, enhances VSV virotherapy and treatment efficacy. Altogether, we show that VSV, either as a stand-alone treatment or in combination with JAK inhibitors provides an effective therapeutic option for ovarian cancer patients. |
| format | Article |
| id | doaj-art-bfcfd51efa8340c9875c1cb70d66a4dd |
| institution | OA Journals |
| issn | 2950-3299 |
| language | English |
| publishDate | 2024-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Oncology |
| spelling | doaj-art-bfcfd51efa8340c9875c1cb70d66a4dd2025-08-20T02:22:32ZengElsevierMolecular Therapy: Oncology2950-32992024-09-0132320082610.1016/j.omton.2024.200826Oncolytic vesicular stomatitis virus alone or in combination with JAK inhibitors is effective against ovarian cancerKaren Geoffroy0Victor Mullins-Dansereau1Kim Leclerc-Desaulniers2Mélissa Viens3Marie-Claude Bourgeois-Daigneault4Cancer and Immunopathology Axes, CHUM Research Centre, Montreal, QC H2X 0A9, Canada; Institut du cancer de Montréal, Montreal, QC H2X 0A9, Canada; Department of Microbiology, Infectious Diseases and Immunology, Faculty of Medicine, University of Montreal, Montreal, QC H3C 3J7, CanadaCancer and Immunopathology Axes, CHUM Research Centre, Montreal, QC H2X 0A9, Canada; Institut du cancer de Montréal, Montreal, QC H2X 0A9, Canada; Department of Microbiology, Infectious Diseases and Immunology, Faculty of Medicine, University of Montreal, Montreal, QC H3C 3J7, CanadaCancer and Immunopathology Axes, CHUM Research Centre, Montreal, QC H2X 0A9, Canada; Institut du cancer de Montréal, Montreal, QC H2X 0A9, CanadaCancer and Immunopathology Axes, CHUM Research Centre, Montreal, QC H2X 0A9, Canada; Institut du cancer de Montréal, Montreal, QC H2X 0A9, Canada; Department of Microbiology, Infectious Diseases and Immunology, Faculty of Medicine, University of Montreal, Montreal, QC H3C 3J7, CanadaCancer and Immunopathology Axes, CHUM Research Centre, Montreal, QC H2X 0A9, Canada; Institut du cancer de Montréal, Montreal, QC H2X 0A9, Canada; Department of Microbiology, Infectious Diseases and Immunology, Faculty of Medicine, University of Montreal, Montreal, QC H3C 3J7, Canada; Corresponding author: Marie-Claude Bourgeois-Daigneault, Cancer and Immunopathology Axes, CHUM Research Centre, Montreal, QC H2X 0A9, Canada.Therapy-resistant ovarian cancers have a poor prognosis and novel effective treatment options are urgently needed. In this study, we evaluated the therapeutic efficacy of the oncolytic vesicular stomatitis virus (VSV) against a panel of patient-derived ovarian cancer cell lines of all epithelial subtypes. Notably, we found that most of the cell lines were sensitive to VSV virotherapy. With the objective of improving treatment efficacy for the oncolytic virus-resistant cell lines, we tested various combinations with ovarian cancer standard of care drugs: olaparib, carboplatin, paclitaxel, doxorubicin, cyclophosphamide, and gemcitabine. While none of these combinations revealed to be beneficial, further experiments demonstrated that the antiviral interferon pathway was functional in VSV-resistant cell lines. Given that interferons signal through Janus kinase (JAK)-STAT to mediate their antiviral function, we tested combinations of oncolytic VSV with clinically relevant JAK inhibitors. Our results show that combining VSV with various JAK inhibitors, including ruxolitinib, enhances VSV virotherapy and treatment efficacy. Altogether, we show that VSV, either as a stand-alone treatment or in combination with JAK inhibitors provides an effective therapeutic option for ovarian cancer patients.http://www.sciencedirect.com/science/article/pii/S2950329924000687ovarian canceroncolytic virusVSVJAK inhibitorsruxolitinib |
| spellingShingle | Karen Geoffroy Victor Mullins-Dansereau Kim Leclerc-Desaulniers Mélissa Viens Marie-Claude Bourgeois-Daigneault Oncolytic vesicular stomatitis virus alone or in combination with JAK inhibitors is effective against ovarian cancer Molecular Therapy: Oncology ovarian cancer oncolytic virus VSV JAK inhibitors ruxolitinib |
| title | Oncolytic vesicular stomatitis virus alone or in combination with JAK inhibitors is effective against ovarian cancer |
| title_full | Oncolytic vesicular stomatitis virus alone or in combination with JAK inhibitors is effective against ovarian cancer |
| title_fullStr | Oncolytic vesicular stomatitis virus alone or in combination with JAK inhibitors is effective against ovarian cancer |
| title_full_unstemmed | Oncolytic vesicular stomatitis virus alone or in combination with JAK inhibitors is effective against ovarian cancer |
| title_short | Oncolytic vesicular stomatitis virus alone or in combination with JAK inhibitors is effective against ovarian cancer |
| title_sort | oncolytic vesicular stomatitis virus alone or in combination with jak inhibitors is effective against ovarian cancer |
| topic | ovarian cancer oncolytic virus VSV JAK inhibitors ruxolitinib |
| url | http://www.sciencedirect.com/science/article/pii/S2950329924000687 |
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