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

Abstract

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.

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