ArticleMolecular therapy : the journal of the American Society of Gene Therapy2023
Pevonedistat, a first-in-class NEDD8-activating enzyme inhibitor, sensitizes cancer cells to VSVΔ51 oncolytic virotherapy.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 22 citations in OpenAlex.
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- Optimization of YF17D-Vectored Zika Vaccine Production by Employing Small-Molecule Viral Sensitizers to Enhance Yields.Vaccines · 2025Article
- Targeting TBK1 potentiates oncolytic virotherapy via amplifying ICAM1-mediated NK cell immunity in chemo-resistant colorectal cancer.Journal for immunotherapy of cancer · 2025Article
- TRIM25: A Global Player of Cell Death Pathways and Promising Target of Tumor-Sensitizing Therapies.Cells · 2025Review
- Neddylation activated TRIM25 desensitizes triple-negative breast cancer to paclitaxel via TFEB-mediated autophagy.Journal of experimental & clinical cancer research : CR · 2024Article
- Article
- Octyl itaconate enhances VSVΔ51 oncolytic virotherapy by multitarget inhibition of antiviral and inflammatory pathways.Nature communications · 2024Article
- Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024Review
- Oncolytic virus and inhibitor for NEDD8-activating enzyme pevonedistat: Promising combination for cancer therapy?Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Unlocking the potential of dimethyl fumarate: enhancing oncolytic HSV-1 efficacy for wider cancer applications.Frontiers in immunology · 2023Article
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16 authors at 2 institutions in 1 country.
Funding
Abstract
The clinical efficacy of VSVΔ51 oncolytic virotherapy has been limited by tumor resistance to viral infection, so strategies to transiently repress antiviral defenses are warranted. Pevonedistat is a first-in-class NEDD8-activating enzyme (NAE) inhibitor currently being tested in clinical trials for its antitumor potential. In this study, we demonstrate that pevonedistat sensitizes human and murine cancer cells to increase oncolytic VSVΔ51 infection, increase tumor cell death, and improve therapeutic outcomes in resistant syngeneic murine cancer models. Increased VSVΔ51 infectivity was also observed in clinical human tumor samples. We further identify the mechanism of this effect to operate via blockade of the type 1 interferon (IFN-1) response through neddylation-dependent interferon-stimulated growth factor 3 (ISGF3) repression and neddylation-independent inhibition of NF-κB nuclear translocation. Together, our results identify a role for neddylation in regulating the innate immune response and demonstrate that pevonedistat can improve the therapeutic outcomes of strategies using oncolytic virotherapy.
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