ArticleClinical cancer research : an official journal of the American Association for Cancer Research2011
A novel oncolytic herpes simplex virus that synergizes with phosphoinositide 3-kinase/Akt pathway inhibitors to target glioblastoma stem cells.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 77 citations in OpenAlex.
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- Advances in oncolytic virus delivery strategies and challenges in clinical translation.Materials today. Bio · 2026Review
- Intracranial injection of genetically modified, mosquito non-transmissible Zika virus: Safety in primates and ramifications for brain tumor therapy.Cell reports. Medicine · 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
- Advanced progress in the genetic modification of the oncolytic HSV-1 virus.Frontiers in oncology · 2024Review
- Photodynamic augmentation of oncolytic virus therapy for central nervous system malignancies.Cancer letters · 2023Article
- Development and application of oncolytic viruses as the nemesis of tumor cells.Frontiers in microbiology · 2023Review
- Oncolytic herpes simplex viruses for the treatment of glioma and targeting glioblastoma stem-like cells.Frontiers in cellular and infection microbiology · 2023Review
- Immunotherapy: a promising approach for glioma treatment.Frontiers in immunology · 2023Review
- Overcoming resistance to oncolytic virus M1 by targeting PI3K-γ in tumor-associated myeloid cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Improving cancer immunotherapy by rationally combining oncolytic virus with modulators targeting key signaling pathways.Molecular cancer · 2022Review
- Review
- Glioblastoma microenvironment and its reprogramming by oncolytic virotherapy.Frontiers in cellular neuroscience · 2022Review
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- Review
- Multiple strategies to improve the therapeutic efficacy of oncolytic herpes simplex virus in the treatment of glioblastoma.Oncology letters · 2021Review
- The Current State of Oncolytic Herpes Simplex Virus for Glioblastoma Treatment.Oncolytic virotherapy · 2021Review
- Oncolytic Herpes Simplex Virus and PI3K Inhibitor BKM120 Synergize to Promote Killing of Prostate Cancer Stem-like Cells.Molecular therapy oncolytics · 2019Article
- Combinatorial Effects of VEGFR Kinase Inhibitor Axitinib and Oncolytic Virotherapy in Mouse and Human Glioblastoma Stem-Like Cell Models.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
purposeTo develop a new oncolytic herpes simplex virus (oHSV) for glioblastoma (GBM) therapy that will be effective in glioblastoma stem cells (GSC), an important and untargeted component of GBM. One approach to enhance oHSV efficacy is by combination with other therapeutic modalities. EXPERIMENTAL
designMG18L, containing a U(S)3 deletion and an inactivating LacZ insertion in U(L)39, was constructed for the treatment of brain tumors. Safety was evaluated after intracerebral injection in HSV-susceptible mice. The efficacy of MG18L in human GSCs and glioma cell lines in vitro was compared with other oHSVs, alone or in combination with phosphoinositide-3-kinase (PI3K)/Akt inhibitors (LY294002, triciribine, GDC-0941, and BEZ235). Cytotoxic interactions between MG18L and PI3K/Akt inhibitors were determined using Chou-Talalay analysis. In vivo efficacy studies were conducted using a clinically relevant mouse model of GSC-derived GBM.
resultsMG18L was severely neuroattenuated in mice, replicated well in GSCs, and had anti-GBM activity in vivo. PI3K/Akt inhibitors displayed significant but variable antiproliferative activities in GSCs, whereas their combination with MG18L synergized in killing GSCs and glioma cell lines, but not human astrocytes, through enhanced induction of apoptosis. Importantly, synergy was independent of inhibitor sensitivity. In vivo, the combination of MG18L and LY294002 significantly prolonged survival of mice, as compared with either agent alone, achieving 50% long-term survival in GBM-bearing mice.
conclusionsThis study establishes a novel therapeutic strategy: oHSV manipulation of critical oncogenic pathways to sensitize cancer cells to molecularly targeted drugs. MG18L is a promising agent for the treatment of GBM, being especially effective when combined with PI3K/Akt pathway-targeted agents.
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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.