Acquired chemoresistance can lead to increased resistance of pancreatic cancer cells to oncolytic vesicular stomatitis virus
Vesicular stomatitis virus (VSV) is a promising oncolytic virus (OV) against different malignancies, including pancreatic ductal adenocarcinoma (PDAC). Our previous studies have demonstrated that VSV-based OVs are effective against the majority of tested human PDAC cell lines. However, some PDAC cel...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-03-01
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| Series: | Molecular Therapy: Oncolytics |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2372770521001686 |
| _version_ | 1798026726844923904 |
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| author | Dakota W. Goad Christian Bressy Molly C. Holbrook Valery Z. Grdzelishvili |
| author_facet | Dakota W. Goad Christian Bressy Molly C. Holbrook Valery Z. Grdzelishvili |
| author_sort | Dakota W. Goad |
| collection | DOAJ |
| description | Vesicular stomatitis virus (VSV) is a promising oncolytic virus (OV) against different malignancies, including pancreatic ductal adenocarcinoma (PDAC). Our previous studies have demonstrated that VSV-based OVs are effective against the majority of tested human PDAC cell lines. However, some PDAC cell lines are resistant to VSV. PDAC is one of the deadliest types of human malignancies in part due to intrinsic or acquired chemoresistance. Here, we investigated how acquired chemoresistance impacts the efficacy of VSV-based OV therapy. Using an experimental evolution approach, we generated PDAC cell lines with increased resistance to gemcitabine and examined their responsiveness to oncolytic virotherapy. We found that gemcitabine-resistant PDAC cells become more resistant to VSV. The cross-resistance correlated with upregulated levels of a subset of interferon-stimulated genes, resembling the interferon-related DNA damage resistance signature (IRDS), often associated with resistance of cancer cells to chemotherapy and/or radiation therapy. Analysis of ten different PDAC cell lines showed that four PDAC cell lines most resistant to VSV were also highly resistant to gemcitabine, and they all displayed IRDS-like expression in our previous reports. Our study highlights a possible interaction between two different therapies that should be considered in the future for the development of rational treatment regimens. |
| first_indexed | 2024-04-11T18:40:00Z |
| format | Article |
| id | doaj.art-a7b2a4a0007042c1af93ae75f8eabf0b |
| institution | Directory Open Access Journal |
| issn | 2372-7705 |
| language | English |
| last_indexed | 2024-04-11T18:40:00Z |
| publishDate | 2022-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Oncolytics |
| spelling | doaj.art-a7b2a4a0007042c1af93ae75f8eabf0b2022-12-22T04:09:02ZengElsevierMolecular Therapy: Oncolytics2372-77052022-03-01245976Acquired chemoresistance can lead to increased resistance of pancreatic cancer cells to oncolytic vesicular stomatitis virusDakota W. Goad0Christian Bressy1Molly C. Holbrook2Valery Z. Grdzelishvili3Department of Biological Sciences, University of North Carolina at Charlotte, 9201 University City Blvd, Charlotte, NC 28223, USADepartment of Biological Sciences, University of North Carolina at Charlotte, 9201 University City Blvd, Charlotte, NC 28223, USADepartment of Biological Sciences, University of North Carolina at Charlotte, 9201 University City Blvd, Charlotte, NC 28223, USADepartment of Biological Sciences, University of North Carolina at Charlotte, 9201 University City Blvd, Charlotte, NC 28223, USA; School of Data Science, University of North Carolina at Charlotte, Charlotte, NC 28223, USA; Corresponding author Valery Z. Grdzelishvili, Department of Biological Sciences, University of North Carolina at Charlotte, 9201 University City Blvd, Charlotte, NC 28223, USA.Vesicular stomatitis virus (VSV) is a promising oncolytic virus (OV) against different malignancies, including pancreatic ductal adenocarcinoma (PDAC). Our previous studies have demonstrated that VSV-based OVs are effective against the majority of tested human PDAC cell lines. However, some PDAC cell lines are resistant to VSV. PDAC is one of the deadliest types of human malignancies in part due to intrinsic or acquired chemoresistance. Here, we investigated how acquired chemoresistance impacts the efficacy of VSV-based OV therapy. Using an experimental evolution approach, we generated PDAC cell lines with increased resistance to gemcitabine and examined their responsiveness to oncolytic virotherapy. We found that gemcitabine-resistant PDAC cells become more resistant to VSV. The cross-resistance correlated with upregulated levels of a subset of interferon-stimulated genes, resembling the interferon-related DNA damage resistance signature (IRDS), often associated with resistance of cancer cells to chemotherapy and/or radiation therapy. Analysis of ten different PDAC cell lines showed that four PDAC cell lines most resistant to VSV were also highly resistant to gemcitabine, and they all displayed IRDS-like expression in our previous reports. Our study highlights a possible interaction between two different therapies that should be considered in the future for the development of rational treatment regimens.http://www.sciencedirect.com/science/article/pii/S2372770521001686vesicular stomatitis virusoncolyticvirotherapypancreatic cancerpancreatic ductal adenocarcinomachemoresistance |
| spellingShingle | Dakota W. Goad Christian Bressy Molly C. Holbrook Valery Z. Grdzelishvili Acquired chemoresistance can lead to increased resistance of pancreatic cancer cells to oncolytic vesicular stomatitis virus Molecular Therapy: Oncolytics vesicular stomatitis virus oncolytic virotherapy pancreatic cancer pancreatic ductal adenocarcinoma chemoresistance |
| title | Acquired chemoresistance can lead to increased resistance of pancreatic cancer cells to oncolytic vesicular stomatitis virus |
| title_full | Acquired chemoresistance can lead to increased resistance of pancreatic cancer cells to oncolytic vesicular stomatitis virus |
| title_fullStr | Acquired chemoresistance can lead to increased resistance of pancreatic cancer cells to oncolytic vesicular stomatitis virus |
| title_full_unstemmed | Acquired chemoresistance can lead to increased resistance of pancreatic cancer cells to oncolytic vesicular stomatitis virus |
| title_short | Acquired chemoresistance can lead to increased resistance of pancreatic cancer cells to oncolytic vesicular stomatitis virus |
| title_sort | acquired chemoresistance can lead to increased resistance of pancreatic cancer cells to oncolytic vesicular stomatitis virus |
| topic | vesicular stomatitis virus oncolytic virotherapy pancreatic cancer pancreatic ductal adenocarcinoma chemoresistance |
| url | http://www.sciencedirect.com/science/article/pii/S2372770521001686 |
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