ArticlePloS one2011
Efficient targeting of head and neck squamous cell carcinoma by systemic administration of a dual uPA and MMP-activated engineered anthrax toxin.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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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.
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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
23 citing papers in PubMed, 36 citations in OpenAlex.
- From pathogenicity to therapy: Investigating the Therapeutic Potential of Bacillus anthracis Anthrax Toxin in Novel Cancer Therapies and Oncological Research.Archives of microbiology · 2025Review
- ERK pathway reactivation prevents anthrax toxin lethality in mice.Nature microbiology · 2025Article
- ATP depletion in anthrax edema toxin pathogenesis.PLoS pathogens · 2025Article
- Review
- Article
- The Urokinase Receptor (uPAR) as a "Trojan Horse" in Targeted Cancer Therapy: Challenges and Opportunities.Cancers · 2021Review
- Targeting the Urokinase-Type Plasminogen Activator Receptor (uPAR) in Human Diseases With a View to Non-invasive Imaging and Therapeutic Intervention.Frontiers in cell and developmental biology · 2021Review
- Inhibitory Effects of a Reengineered Anthrax Toxin on Canine and Human Osteosarcoma Cells.Toxins · 2020Article
- Article
- Discretionary Transduction of MMP-Sensitized Tousled in Head and Neck Cancer.Molecular therapy oncolytics · 2019Article
- Bismaleimide cross-linked anthrax toxin forms functional octamers with high specificity in tumor targeting.Protein science : a publication of the Protein Society · 2019Article
- Article
- Mitogen-activated protein kinase signaling pathway in oral cancer.Oncology letters · 2018Article
- Anti-tumor activity of anthrax toxin variants that form a functional translocation pore by intermolecular complementation.Oncotarget · 2017Article
- Solid tumor therapy by selectively targeting stromal endothelial cells.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Tumor Targeting and Drug Delivery by Anthrax Toxin.Toxins · 2016Review
- An anthrax toxin variant with an improved activity in tumor targeting.Scientific reports · 2015Article
- Targeting the membrane-anchored serine protease testisin with a novel engineered anthrax toxin prodrug to kill tumor cells and reduce tumor burden.Oncotarget · 2015Article
- Comparative toxicity and efficacy of engineered anthrax lethal toxin variants with broad anti-tumor activities.Toxicology and applied pharmacology · 2014Article
- Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Although considerable progress has been made in elucidating the etiology of the disease, the prognosis for individuals diagnosed with HNSCC remains poor, underscoring the need for development of additional treatment modalities. HNSCC is characterized by the upregulation of a large number of proteolytic enzymes, including urokinase plasminogen activator (uPA) and an assortment of matrix metalloproteinases (MMPs) that may be expressed by tumor cells, by tumor-supporting stromal cells or by both. Here we explored the use of an intercomplementing anthrax toxin that requires combined cell surface uPA and MMP activities for cellular intoxication and specifically targets the ERK/MAPK pathway for the treatment of HNSCC. We found that this toxin displayed strong systemic anti-tumor activity towards a variety of xenografted human HNSCC cell lines by inducing apoptotic and necrotic tumor cell death, and by impairing tumor cell proliferation and angiogenesis. Interestingly, the human HNSCC cell lines were insensitive to the intercomplementing toxin when cultured ex vivo, suggesting that either the toxin targets the tumor-supporting stromal cell compartment or that the tumor cell requirement for ERK/MAPK signaling differs in vivo and ex vivo. This intercomplementing toxin warrants further investigation as an anti-HNSCC agent.
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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.