ArticleMolecular therapy : the journal of the American Society of Gene Therapy2013
Multimechanistic tumor targeted oncolytic virus overcomes resistance in brain tumors.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 56 citations in OpenAlex.
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- Delineated domain of VP2 capsid protein in H-1 parvovirus that determines susceptibility to human cancer cells.Journal of microbiology (Seoul, Korea) · 2026Article
- The promise of immunotherapy for central nervous system tumours.Nature reviews. Immunology · 2026Review
- Mechanisms of Oncolytic Virus-Induced Multi-Modal Cell Death and Therapeutic Prospects.International journal of molecular sciences · 2025Review
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- Ti-Based Metallic Biomaterials for Antitumor Applications.Materials (Basel, Switzerland) · 2025Review
- Novel Therapies in Glioblastoma Treatment: Review of Glioblastoma; Current Treatment Options; and Novel Oncolytic Viral Therapies.Medical sciences (Basel, Switzerland) · 2023Review
- Combined effect of the pro-apoptotic rhTRAIL protein and HSV-1 virus in head and neck cancer cell lines.Scientific reports · 2023Article
- Recent Developments in Glioblastoma Therapy: Oncolytic Viruses and Emerging Future Strategies.Viruses · 2023Review
- Oncolytic herpes simplex viruses for the treatment of glioma and targeting glioblastoma stem-like cells.Frontiers in cellular and infection microbiology · 2023Review
- Nanobody-based retargeting of an oncolytic herpesvirus for eliminating CXCR4Molecular therapy oncolytics · 2022Article
- Immunology Meets Bioengineering: Improving the Effectiveness of Glioblastoma Immunotherapy.Cancers · 2022Review
- Quantitative imaging of apoptosis following oncolytic virotherapy by magnetic resonance fingerprinting aided by deep learning.Nature biomedical engineering · 2022Article
- High accumulation of Mx2 renders limited multiplication of oncolytic herpes simplex virus-1 in human tumor cells.Scientific reports · 2021Article
- Review
- Review
- The Current State of Oncolytic Herpes Simplex Virus for Glioblastoma Treatment.Oncolytic virotherapy · 2021Review
- Multivariate genome wide association and network analysis of subcortical imaging phenotypes in Alzheimer's disease.BMC genomics · 2020Article
- lncRNA TPTEP1 inhibits stemness and radioresistance of glioma through miR‑106a‑5p‑mediated P38 MAPK signaling.Molecular medicine reports · 2020Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Only a subset of cancer patients inoculated with oncolytic herpes simplex virus (oHSV) type-1 has shown objective response in phase 1 and 2 clinical trials. This has raised speculations whether resistance of tumor cells to oHSV therapy may be a limiting factor. In this study, we have identified established and patient derived primary glioblastoma multiforme (GBM) stem cell lines (GSC) resistant to oHSV and also to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) that has recently shown promise in preclinical and initial clinical studies. We created a recombinant oHSV bearing a secretable TRAIL (oHSV-TRAIL) and hypothesized that oHSV-TRAIL could be used as a cancer therapeutic to target a broad spectrum of resistant tumors in a mechanism-based manner. Using the identified resistant GBM lines, we show that oHSV-TRAIL downregulates extracellular signal-regulated protein kinase (ERK)-mitogen-activated protein kinase (MAPK) and upregulates c-Jun N-terminal kinase (JNK) and p38-MAPK signaling, which primes resistant GBM cells to apoptosis via activation of caspase-8, -9, and -3. We further show that oHSV-TRAIL inhibits tumor growth and invasiveness and increases survival of mice bearing resistant intracerebral tumors without affecting the normal tissues. This study sheds new light on the mechanism by which oHSV and TRAIL function in concert to overcome therapeutic-resistance, and provides an oncolytic virus based platform to target a broad spectrum of different cancer types.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.