scholarly journals Novel tumor suppressor microRNA at frequently deleted chromosomal region 8p21 regulates Epidermal Growth Factor Receptor in prostate cancer

Oncotarget ◽  
2016 ◽  
Vol 7 (43) ◽  
pp. 70388-70403 ◽  
Author(s):  
Nathan Bucay ◽  
Kirandeep Sekhon ◽  
Shahana Majid ◽  
Soichiro Yamamura ◽  
Varahram Shahryari ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Tumor Suppressor ◽  
Epidermal Growth Factor ◽  
Chromosomal Region ◽  
Growth Factor Receptor ◽  
Epidermal Growth

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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