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Effects of EGFR tyrosine kinase inhibitor erlotinib in prostate cancer cells in vitro
The Prostate, 06/30/09
Festuccia C et al. - In a study to determine why EGFR inhibitors been so ineffective in human prostate cancer (PCa), the results seem to suggest that a low EGFR/Her2 ratio and PTEN absence are the main factors responsible of erlotinib inefficacy. The inhibition of EGFR could have important antitumor effects in hormone-naive rather than in hormonally treated pts.
Methods- The effectiveness of erlotinib was assessed in a wide range of PCa cells (wild type or engineered to overexpress peculiar proteins including androgen receptor and PTEN).
- The effectiveness of erlotinib was inversely correlated to the EGFR/Her2 ratio rather than EGFR/p-EGFR or Her2/p-Her2 levels.
- Chronic treatment with bicalutamide induced overexpression of Her2 and reduction of EGFR/Her2 ratio and this was associated with increased Akt and Erk activity.
- In these treatment conditions, a reduced efficacy of erlotinib was observed.
- At the same time, an increased efficacy vs erlotinib was documented in cancer cells chronically exposed to DHT.
- In these culture conditions, low levels of Her2 and increased EGFR/Her2 ratio were evidenced.
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