scholarly journals Epidermal Growth Factor Receptor Status in Circulating Tumor Cells as a Predictive Biomarker of Sensitivity in Castration-Resistant Prostate Cancer Patients Treated with Docetaxel Chemotherapy

2016 ◽  
Vol 17 (12) ◽  
pp. 2008 ◽  
Author(s):  
Takatsugu Okegawa ◽  
Naoshi Itaya ◽  
Hidehiko Hara ◽  
Mitsuhiro Tambo ◽  
Kikuo Nutahara
Keyword(s):  
Prostate Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Predictive Biomarker ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Epidermal Growth ◽  
Docetaxel Chemotherapy

scholarly journals Pseudomonas Exotoxin A Based Toxins Targeting Epidermal Growth Factor Receptor for the Treatment of Prostate Cancer

Toxins ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 753
Author(s):  
Alexandra Fischer ◽  
Isis Wolf ◽  
Hendrik Fuchs ◽  
Anie Priscilla Masilamani ◽  
Philipp Wolf
Keyword(s):  
Prostate Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Exotoxin A ◽  
Pseudomonas Exotoxin ◽  
Pseudomonas Exotoxin A ◽  
Epidermal Growth ◽  
Targeted Toxins

The epidermal growth factor receptor (EGFR) was found to be a valuable target on prostate cancer (PCa) cells. However, EGFR inhibitors mostly failed in clinical studies with patients suffering from PCa. We therefore tested the targeted toxins EGF-PE40 and EGF-PE24mut consisting of the natural ligand EGF as binding domain and PE40, the natural toxin domain of Pseudomonas Exotoxin A, or PE24mut, the de-immunized variant thereof, as toxin domains. Both targeted toxins were expressed in the periplasm of E.coli and evoked an inhibition of protein biosynthesis in EGFR-expressing PCa cells. Concentration- and time-dependent killing of PCa cells was found with IC50 values after 48 and 72 h in the low nanomolar or picomolar range based on the induction of apoptosis. EGF-PE24mut was found to be about 11- to 120-fold less toxic than EGF-PE40. Both targeted toxins were more than 600 to 140,000-fold more cytotoxic than the EGFR inhibitor erlotinib. Due to their high and specific cytotoxicity, the EGF-based targeted toxins EGF-PE40 and EGF-PE24mut represent promising candidates for the future treatment of PCa.

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