4.3 Article

Epidermal Growth Factor Based Targeted Toxin for the Treatment of Bladder Cancer

Journal

ANTICANCER RESEARCH
Volume 41, Issue 8, Pages 3741-3746

Publisher

INT INST ANTICANCER RESEARCH
DOI: 10.21873/anticanres.15165

Keywords

Bladder cancer; epidermal growth factor; epidermal growth factor receptor; targeted toxin; Pseudomonas Exotoxin A

Categories

Funding

  1. German Research Foundation [WO 2178/2-1]

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The study developed a targeted toxin EGF-PE40, which showed significant cytotoxicity against EGFR-expressing bladder cancer cells with high specificity. The results indicated that EGF-PE40 could induce apoptosis to kill the bladder cancer cells effectively, suggesting its potential as a promising candidate for future bladder cancer treatment.
Background/Aim: Reports on over-expression of the epidermal growth factor receptor (EGFR) in bladder cancer and its function in tumorigenesis have suggested to target this antigen. Materials and Methods: We generated the targeted toxin EGF-PE40 consisting of the human epidermal growth factor (EGF) as the binding domain and PE40, a truncated version of Pseudomonas Exotoxin A, as the toxin domain. EGF-PE40 was tested on EGFR-expressing bladder cancer cells in view of binding via flow cytometry, and cytotoxicity via WST viability assay. Induction of apoptosis was examined by western blot. Results: The targeted toxin specifically triggered cytotoxicity in the bladder cancer cells with 50% inhibitory concentration (IC50) values in the low nanomolar or picomolar range, and was about 1,250-to 1,500-fold more cytotoxic than the EGFR inhibitor erlotinib. Cytotoxicity of EGF-PE40 was based on the induction of apoptosis. Conclusion: EGF-PE40 represents a promising candidate for the future treatment of bladder cancer.

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