Involvement of Growth Factor Receptors of the Epidermal Growth Factor Receptor Family in Prostate Cancer Development and Progression to Androgen Independence

2003 ◽  
Vol 2 (1) ◽  
pp. 50-57 ◽  
Author(s):  
Giuseppe Di Lorenzo ◽  
Roberto Bianco ◽  
Giampaolo Tortora ◽  
Fortunato Ciardiello
Keyword(s):  
Prostate Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Cancer Development ◽  
Androgen Independence ◽  
Prostate Cancer Development ◽  
Epidermal Growth ◽  
Receptor Family

Critical Update and Emerging Trends in Epidermal Growth Factor Receptor Targeting in Cancer

2005 ◽  
Vol 23 (11) ◽  
pp. 2445-2459 ◽  
Author(s):  
José Baselga ◽  
Carlos L. Arteaga
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Egfr Gene ◽  
Epidermal Growth ◽  
Egfr Tkis ◽  
Receptor Family

The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase of the ErbB receptor family that is abnormally activated in many epithelial tumors. The aberrant activation of the EGFR leads to enhanced proliferation and other tumor-promoting activities, which provide a strong rationale to target this receptor family. There are two classes of anti-EGFR agents: monoclonal antibodies (MAbs) directed at the extracellular domain of the receptor and small molecule, adenosine triphosphate–competitive inhibitors of the receptor's tyrosine kinase. Anti-EGFR MAbs have shown antitumor activity in advanced colorectal carcinoma, squamous cell carcinomas of the head and neck, non–small-cell lung cancer (NSCLC) and renal cell carcinomas. The tyrosine kinase inhibitors (TKIs) have a partially different activity profile. They are active against NSCLC, and a specific EGFR inhibitor has shown improvement in survival. Recently, mutations and amplifications of the EGFR gene have been identified in NSCLC and predict for enhanced sensitivity to anti-EGFR TKIs. In addition to specific anti-EGFR TKIs, there are broader acting inhibitors such as dual EGFR HER-2 inhibitors and combined anti-pan-ErbB and antivascular endothelial growth factor receptor inhibitors. Current research efforts are directed at selecting the optimal dose and schedule and identifying predictive factors of response and resistance beyond EGFR gene mutations and/or amplifications. Finally, there is a need for improved strategies to integrate anti-EGFR agents with conventional therapies and to explore combinations with other molecular targeted approaches including other antireceptor therapies, receptor-downstream signaling transduction inhibitors, and targeted approaches interfering with other essential drivers of cancer, such as angiogenesis.

scholarly journals Ligand-specific activation of HER4/p180erbB4, a fourth member of the epidermal growth factor receptor family.

1993 ◽  
Vol 90 (5) ◽  
pp. 1746-1750 ◽  
Author(s):  
G. D. Plowman ◽  
J. M. Culouscou ◽  
G. S. Whitney ◽  
J. M. Green ◽  
G. W. Carlton ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Epidermal Growth ◽  
Fourth Member ◽  
Receptor Family

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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