ArticlePloS one2013
Combination treatments with the PKC inhibitor, enzastaurin, enhance the cytotoxicity of the anti-mesothelin immunotoxin, SS1P.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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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
9 citing papers in PubMed, 14 citations in OpenAlex.
- Review
- Mesothelin-Targeted Recombinant Immunotoxins for Solid Tumors.Biomolecules · 2020Review
- The Role of Mesothelin as a Diagnostic and Therapeutic Target in Pancreatic Ductal Adenocarcinoma: A Comprehensive Review.Targeted oncology · 2018Review
- Targeting a Cancer-Specific Epitope of the Epidermal Growth Factor Receptor in Triple-Negative Breast Cancer.Journal of the National Cancer Institute · 2016Article
- Effects of inhibitors of vascular endothelial growth factor receptor 2 and downstream pathways of receptor tyrosine kinases involving phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin or mitogen-activated protein kinase in canine hemangiosarcoma cell lines.Canadian journal of veterinary research = Revue canadienne de recherche veterinaire · 2016Article
- Chemical Screens Identify Drugs that Enhance or Mitigate Cellular Responses to Antibody-Toxin Fusion Proteins.PloS one · 2016Article
- Mechanisms of action of therapeutic antibodies for cancer.Molecular immunology · 2015Review
- Phosphorylation of Nonmuscle myosin II-A regulatory light chain resists Sendai virus fusion with host cells.Scientific reports · 2015Article
- The development of immunoconjugates for targeted cancer therapy.Nature reviews. Clinical oncology · 2014Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Activated protein kinase C (PKC) contributes to tumor survival and proliferation, provoking the development of inhibitory agents as potential cancer therapeutics. Immunotoxins are antibody-based recombinant proteins that employ antibody fragments for cancer targeting and bacterial toxins as the cytotoxic agent. Pseudomonas exotoxin-based immunotoxins act via the ADP-ribosylation of EF2 leading to the enzymatic inhibition of protein synthesis. Combining PKC inhibitors with the immunotoxin SS1P, targeted to surface mesothelin, was undertaken to explore possible therapeutic strategies. Enzastaurin but not two other PKC inhibitors combined with SS1P to produce synergistic cell death via apoptosis. Mechanistic insights of the synergistic killing centered on the complete loss of the prosurvival Bcl2 protein, Mcl-1, the loss of AKT and the activation of caspase 3/7. Synergy was most evident when cells exhibited resistance to the immunotoxin alone. Further, because PKC inhibition by itself was not sufficient to enhance SS1P action, enzastaurin must target other kinases that are involved in the immunotoxin pathway.
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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.