ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014
Bortezomib-induced unfolded protein response increases oncolytic HSV-1 replication resulting in synergistic antitumor effects.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 76 citations in OpenAlex.
- A phase II trial evaluating the effects and intra-tumoral penetration of bortezomib in patients with recurrent malignant gliomas.Journal of neuro-oncology · 2016Trial
- ATF4: Orchestrating Cellular Stress Adaptation, Metabolism, and Immune Regulation in Health and Disease.International journal of molecular sciences · 2026Review
- UPR/ATF4/Noxa pathway overactivation through SERCA2 inhibition or ONC201 treatment combined with ABT-737 triggers apoptosis in chemoresistant ovarian cancer cells and patient-derived tumor organoids.Cell death & disease · 2026Article
- Advancements on the synergistic application of oncolytic viruses and molecularly targeted therapies for the treatment of solid tumors (Review).International journal of oncology · 2026Review
- A systematic review on the potential of modulating the IRE arm of the UPR in U87 and U251 glioblastoma cells for improved therapeutic efficacy.Molecular biology research communications · 2026Review
- Oncolytic viruses in head and neck cancer: therapeutic promise and translational challenges.Frontiers in immunology · 2026Review
- Review
- Oncolytic HSV and cancer drug interactions: Current clinical status and future directions.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- TRIM56 enhances adenoviral E1A steady state to improve oncolytic adenovirus therapy efficacy.Journal of virology · 2025Article
- Viral warfare: unleashing engineered oncolytic viruses to outsmart cancer's defenses.Frontiers in immunology · 2025Review
- Tracing from Periphery to Cortex: Application of Herpes Simplex Virus to Somatosensory Neural Networks.Neuroscience bulletin · 2024Article
- Harnessing machine learning to find synergistic combinations for FDA-approved cancer drugs.Scientific reports · 2024Article
- The combination therapy of oncolytic virotherapy.Frontiers in pharmacology · 2024Review
- Targeting endoplasmic reticulum stress signaling in ovarian cancer therapy.Cancer biology & medicine · 2023Review
- Oncolytic herpes simplex virus armed with a bacterial GBP1 degrader improves antitumor activity.Molecular therapy oncolytics · 2023Article
- Oncolytic virotherapy: basic principles, recent advances and future directions.Signal transduction and targeted therapy · 2023Review
- Targeting TMEM205 mediated drug resistance in ovarian clear cell carcinoma using oncolytic virus.Journal of ovarian research · 2022Article
- Emetine in Combination with Chloroquine Induces Oncolytic Potential of HIV-1-Based Lentiviral Particles.Cells · 2022Article
- Immunogenic cell death: The cornerstone of oncolytic viro-immunotherapy.Frontiers in immunology · 2022Review
- Current strategies in engaging oncolytic viruses with antitumor immunity.Molecular therapy oncolytics · 2021Review
Corrections and comments
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Authors and funding
16 authors at 7 institutions in 1 country.
Funding
Abstract
backgroundBortezomib is an FDA-approved proteasome inhibitor, and oncolytic herpes simplex virus-1 (oHSV) is a promising therapeutic approach for cancer. We tested the impact of combining bortezomib with oHSV for antitumor efficacy. EXPERIMENTAL
designThe synergistic interaction between oHSV and bortezomib was calculated using Chou-Talalay analysis. Viral replication was evaluated using plaque assay and immune fluorescence. Western blot assays were used to evaluate induction of estrogen receptor (ER) stress and unfolded protein response (UPR). Inhibitors targeting Hsp90 were utilized to investigate the mechanism of cell killing. Antitumor efficacy in vivo was evaluated using subcutaneous and intracranial tumor xenografts of glioma and head and neck cancer. Survival was analyzed by Kaplan-Meier curves and two-sided log-rank test.
resultsCombination treatment with bortezomib and oHSV (34.5ENVE), displayed strong synergistic interaction in ovarian cancer, head and neck cancer, glioma, and malignant peripheral nerve sheath tumor (MPNST) cells. Bortezomib treatment induced ER stress, evident by strong induction of Grp78, CHOP, PERK, and IRE1α (Western blot analysis) and the UPR (induction of hsp40, 70, and 90). Bortezomib treatment of cells at both sublethal and lethal doses increased viral replication (P < 0.001), but inhibition of Hsp90 ablated this response, reducing viral replication and synergistic cell killing. The combination of bortezomib and 34.5ENVE significantly enhanced antitumor efficacy in multiple different tumor models in vivo.
conclusionsThe dramatic synergy of bortezomib and 34.5ENVE is mediated by bortezomib-induced UPR and warrants future clinical testing in patients.
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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.