ArticleNeuro-oncology2019
Oncolytic HSV therapy increases trametinib access to brain tumors and sensitizes them in vivo.
Article in Neuro-oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 50 citations in OpenAlex.
- Leveraging multimodal cancer immunotherapy to amplify the efficacy of oncolytic viruses.Experimental hematology & oncology · 2026Review
- Advancements on the synergistic application of oncolytic viruses and molecularly targeted therapies for the treatment of solid tumors (Review).International journal of oncology · 2026Review
- CD73 blockade enhances antitumor efficacy of oHSV in solid tumors by increasing macrophage-mediated antigen presentation.Journal for immunotherapy of cancer · 2026Article
- Oncolytic virus-induced IL-1βJournal for immunotherapy of cancer · 2025Article
- SWI/SNF complexes govern ontology-specific transcription factor function in MYC-subtype atypical teratoid rhabdoid tumor.Neuro-oncology · 2025Article
- Oncolytic HSV and cancer drug interactions: Current clinical status and future directions.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Review
- Review
- Oncolytic immunovirotherapy: finding the tumor antigen needle in the antiviral haystack.Immunotherapy · 2025Review
- Blocking Feedback Immunosuppression of Antigen Presentation in Brain Tumor During Oncolytic Virotherapy with oHSV-mshPKR.Molecular cancer therapeutics · 2025Article
- Low-frequency magnetic field therapy for glioblastoma: Current advances, mechanisms, challenges and future perspectives.Journal of advanced research · 2025Review
- Metabolism: an important player in glioma survival and development.Discover oncology · 2024Review
- Advances in antitumour therapy with oncolytic herpes simplex virus combinations.Discover oncology · 2024Review
- Oncolytic virotherapy: basic principles, recent advances and future directions.Signal transduction and targeted therapy · 2023Review
- Oncolytic herpes simplex viruses for the treatment of glioma and targeting glioblastoma stem-like cells.Frontiers in cellular and infection microbiology · 2023Review
- Targeting Options of Tumor-Associated Macrophages (TAM) Activity in Gliomas.Current neuropharmacology · 2023Review
- Immunosuppressive cells in oncolytic virotherapy for glioma: challenges and solutions.Frontiers in cellular and infection microbiology · 2023Review
- Cell-based and cell-free immunotherapies for glioblastoma: current status and future directions.Frontiers in immunology · 2023Review
- Protein Kinase Inhibitors as a New Target for Immune System Modulation and Brain Cancer Management.International journal of molecular sciences · 2022Review
- In Vitro/In Vivo Translation of Synergistic Combination of MDM2 and MEK Inhibitors in Melanoma Using PBPK/PD Modelling: Part II.International journal of molecular sciences · 2022Article
Corrections and comments
- Commented on by
Authors and funding
16 authors at 7 institutions in 1 country.
Funding
Abstract
backgroundHyperactivation of the RAS-RAF-MEK-ERK signaling pathway is exploited by glioma cells to promote their growth and evade apoptosis. MEK activation in tumor cells can increase replication of ICP34.5-deleted herpes simplex virus type 1 (HSV-1), but paradoxically its activation in tumor-associated macrophages promotes a pro-inflammatory signaling that can inhibit virus replication and propagation. Here we investigated the effect of blocking MEK signaling in conjunction with oncolytic HSV-1 (oHSV) for brain tumors.
methodsInfected glioma cells co-cultured with microglia or macrophages treated with or without trametinib were used to test trametinib effect on macrophages/microglia. Enzyme-linked immunosorbent assay, western blotting, and flow cytometry were utilized to evaluate the effect of the combination therapy. Pharmacokinetic (PK) analysis of mouse plasma and brain tissue was used to evaluate trametinib delivery to the CNS. Intracranial human and mouse glioma-bearing immune deficient and immune competent mice were used to evaluate the antitumor efficacy.
resultOncolytic HSV treatment rescued trametinib-mediated feedback reactivation of the mitogen-activated protein kinase signaling pathway in glioma. In vivo, PK analysis revealed enhanced blood-brain barrier penetration of trametinib after oHSV treatment. Treatment by trametinib, a MEK kinase inhibitor, led to a significant reduction in microglia- and macrophage-derived tumor necrosis factor alpha (TNFα) secretion in response to oHSV treatment and increased survival of glioma-bearing mice. Despite the reduced TNFα production observed in vivo, the combination treatment activated CD8+ T-cell mediated immunity and increased survival in a glioma-bearing immune-competent mouse model.
conclusionThis study provides a rationale for combining oHSV with trametinib for the treatment of brain tumors.
Indexed as
Identifiers
What OpenQuestion holds
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.