ArticleCancer gene therapy2011
An oncolytic adenovirus defective in pRb-binding (dl922-947) can efficiently eliminate pancreatic cancer cells and tumors in vivo in combination with 5-FU or gemcitabine.
Article in Cancer gene therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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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.
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Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- A Phase I clinical trial of EUS-guided intratumoral injection of the oncolytic virus, HF10 for unresectable locally advanced pancreatic cancer.BMC cancer · 2018Trial
- Development of a novel oncolytic adenovirus controlled by CDX2 promoter for esophageal adenocarcinoma therapy.Journal of gastroenterology · 2024Article
- The role of viruses in cancer development versus cancer therapy: An oncological perspective.Cancer medicine · 2023Review
- Oncolytic virotherapy: basic principles, recent advances and future directions.Signal transduction and targeted therapy · 2023Review
- Review
- Microorganisms in chemotherapy for pancreatic cancer: An overview of current research and future directions.International journal of biological sciences · 2021Review
- Pharmacological Inhibition of WEE1 Potentiates the Antitumoral Effect of theInternational journal of molecular sciences · 2020Article
- Virotherapy as a Potential Therapeutic Approach for the Treatment of Aggressive Thyroid Cancer.Cancers · 2019Review
- Systemic delivery and SPECT/CT in vivo imaging ofScientific reports · 2019Article
- Polyethylenimine (PEI)-Mediated E1A Increases the Sensitivity of Hepatocellular Carcinoma Cells to Chemotherapy.Medical science monitor basic research · 2019Article
- The Oncolytic VirusFrontiers in oncology · 2019Article
- Designer Oncolytic Adenovirus: Coming of Age.Cancers · 2018Review
- Combination of interferon-expressing oncolytic adenovirus with chemotherapy and radiation is highly synergistic in hamster model of pancreatic cancer.Oncotarget · 2018Article
- Article
- Gene Therapy for Pancreatic Cancer: Specificity, Issues and Hopes.International journal of molecular sciences · 2017Review
- Histone deacetylase inhibitor trichostatin A enhances the antitumor effect of the oncolytic adenovirus H101 on esophageal squamous cell carcinomaOncology letters · 2017Article
- Genomic Signature of the Natural Oncolytic Herpes Simplex Virus HF10 and Its Therapeutic Role in Preclinical and Clinical Trials.Frontiers in oncology · 2017Review
- E1A-engineered human umbilical cord mesenchymal stem cells as carriers and amplifiers for adenovirus suppress hepatocarcinoma in mice.Oncotarget · 2016Article
- The E1B19K-deleted oncolytic adenovirus mutant AdΔ19K sensitizes pancreatic cancer cells to drug-induced DNA-damage by down-regulating Claspin and Mre11.Oncotarget · 2016Article
- Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Pancreatic adenocarcinoma has a poor prognosis and frequently develops resistance to standard chemotherapeutics. Oncolytic adenoviruses represent a promising approach to overcome treatment resistance. The replication-selective dl922-947 adenovirus, defective in pRb binding, targets cancers with deregulated cell cycle control, such as the majority of pancreatic tumors. Cell killing efficacy was higher for dl922-947 than for adenovirus type 5 (Ad5) and the clinically approved dl1520 in pancreatic cancer cells with K-ras, p16 and p53 mutations. Combinations of dl922-947 and 5-fluorouracil or gemcitabine (2'2'-difluoro-2-deoxytidine) resulted in strong synergistic cell killing in Suit-2 and the highly drug- and virus-resistant Hs766T cells. Viral uptake increased in response to drugs, but was independent of the expression levels of the viral attachment receptor coxsackie and adenovirus receptor (CAR), whereas expression levels of the internalization receptors α(v)β(3)- and α(v)β(5)-integrins were increased. Early viral E1A expression was potently induced with drugs contributing to the synergistic effects. The dl922-947 mutant was more efficacious than Ad5 in vivo in Hs766T and Suit-2 xenograft models. In combination with gemcitabine, median survival was further prolonged. We demonstrate that dl922-947 is highly efficacious in pancreatic cancers and conclude that oncolytic adenoviruses harboring the E1ACR2 deletion have great potential for development into future clinical candidates for pancreatic cancer.
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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.