ArticleInternational journal of cancer2013
Hemangiosarcoma and its cancer stem cell subpopulation are effectively killed by a toxin targeted through epidermal growth factor and urokinase receptors.
Article in International journal of cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 39 citations in OpenAlex.
- Remodeling the sarcoma microenvironment by simultaneous targeting of urokinase-type plasminogen activator receptors and epidermal growth factor receptors to promote antitumor activity.The Journal of pharmacology and experimental therapeutics · 2025Article
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- Blocking tri-methylguanosine synthase 1 (TGS1) stops anchorage-independent growth of canine sarcomas.Cancer gene therapy · 2023Article
- Antitumor Activity of an Anti-EGFR/HER2 Bispecific Antibody in a Mouse Xenograft Model of Canine Osteosarcoma.Pharmaceutics · 2022Article
- LukS-PV inhibits hepatocellular carcinoma cells migration by downregulating HDAC6 expression.BMC cancer · 2022Article
- Urokinase-type plasminogen activator receptor (uPAR) as a therapeutic target in cancer.Journal of translational medicine · 2022Review
- Review
- Retrospective evaluation of thrombocytopenia and tumor stage as prognostic indicators in dogs with splenic hemangiosarcoma.Journal of the American Veterinary Medical Association · 2021Article
- Impact of repeated cycles of EGF bispecific angiotoxin (eBAT) administered at a reduced interval from doxorubicin chemotherapy in dogs with splenic haemangiosarcoma.Veterinary and comparative oncology · 2020Article
- Targeting Receptors on Cancer Cells with Protein Toxins.Biomolecules · 2020Review
- Bispecific Targeting of EGFR and Urokinase Receptor (uPAR) Using Ligand-Targeted Toxins in Solid Tumors.Biomolecules · 2020Review
- Determination of urokinase-type plasminogen activator serum levels in healthy and oncologic cats.Canadian journal of veterinary research = Revue canadienne de recherche veterinaire · 2020Article
- Anticancer effects of resveratrol in canine hemangiosarcoma cell lines.Veterinary and comparative oncology · 2018Article
- Modulation of fatty acid metabolism and immune suppression are features of in vitro tumour sphere formation in ontogenetically distinct dog cancers.Veterinary and comparative oncology · 2018Article
- Article
- Targeting pediatric sarcoma with a bispecific ligand immunotoxin targeting urokinase and epidermal growth factor receptors.Oncotarget · 2018Article
- Targeting EGFR and uPAR on human rhabdomyosarcoma, osteosarcoma, and ovarian adenocarcinoma with a bispecific ligand-directed toxin.Clinical pharmacology : advances and applications · 2018Article
- Strong radioprotective FGF1 signaling down-regulates proliferative and metastatic capabilities of the angiosarcoma cell line, ISOS-1, through the dual inhibition of EGFR and VEGFR pathways.Clinical and translational radiation oncology · 2017Article
- Serum levels of urokinase-type plasminogen activator in healthy dogs and oncologic canine patients.Veterinary world · 2017Article
Corrections and comments
- Erratum issuedErratum.2018
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Targeted toxins have the potential to overcome intrinsic or acquired resistance of cancer cells to conventional cytotoxic agents. Here, we hypothesized that EGFuPA-toxin, a bispecific ligand-targeted toxin (BLT) consisting of a deimmunized Pseudomonas exotoxin (PE) conjugated to epidermal growth factor and urokinase, would efficiently target and kill cells derived from canine hemangiosarcoma (HSA), a highly chemotherapy resistant tumor, as well as cultured hemangiospheres, used as a surrogate for cancer stem cells (CSC). EGFuPA-toxin showed cytotoxicity in four HSA cell lines (Emma, Frog, DD-1 and SB) at a concentration of ≤100 nM, and the cytotoxicity was dependent on specific ligand-receptor interactions. Monospecific targeted toxins also killed these chemoresistant cells; in this case, a "threshold" level of EGFR expression appeared to be required to make cells sensitive to the monospecific EGF-toxin, but not to the monospecific uPA-toxin. The IC₅₀ of CSCs was higher by approximately two orders of magnitude as compared to non-CSCs, but these cells were still sensitive to EGFuPA-toxin at nanomolar (i.e., pharmacologically relevant) concentrations, and when targeted by EGFuPA-toxin, resulted in death of the entire cell population. Taken together, our results support the use of these toxins to treat chemoresistant tumors such as sarcomas, including those that conform to the CSC model. Our results also support the use of companion animals with cancer for further translational development of these cytotoxic molecules.
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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.