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Antitumor effects of carnertinib in castration resistant prostate cancer models: A comparative study with erlotinib
Author(s) -
Gravina Giovanni Luca,
Marampon Francesco,
Piccolella Margherita,
Biordi Leda,
Ficorella Corrado,
Motta Marcella,
Jannini Emmanuele A.,
Tombolini Vincenzo,
Festuccia Claudio
Publication year - 2011
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.21363
Subject(s) - erlotinib , bicalutamide , prostate cancer , medicine , androgen receptor , cancer research , pharmacology , egfr inhibitors , in vivo , oncology , cancer , epidermal growth factor receptor , biology , microbiology and biotechnology
BACKGROUND AND PURPOSE Although preclinical results suggest that the inhibition of erb‐B1 or erb‐B2 can be an useful tool to castration resistant prostate cancer (CRPC), neither inhibitor demonstrated to provide benefit in this category of patient. Here, we compared the effects of erlotinib, a specific EGFR inhibitor, with those observed with Carnertinib, an orally available pan‐erbB receptor inhibitor, in a wide panel of hormone sensitive and independent prostate cancer cell lines. MATERIALS AND METHODS Variation in proliferation rate, cell cycle, and apoptosis after erlotinib and carnertinib treatments will be evaluated in vitro. In vivo experiments were performed using two models of CRPC, 22rv1 (AR expressing), and PC3 (AR negative) cell lines grown in nude mice. Intact nude mice bearing 22rv1 cells also received bicalutamide (BCLT) in combination with anti‐target agents. RESULTS Here, we found that Erlotinib and carnertinib effectiveness was positively related to expression and activation levels of Her2, whereas erlotinib effectiveness was influenced to the EGFR/Her2 ratio resulting more effective when EGFR levels were significantly higher of Her2. Overall, in vitro carnertinib efficacy was higher than those observed with erlotinib. The combination between erlotinib and androgen deprivation therapy or BCLT showed no significant effects when compared to single treatments whereas carnertinib was active in presence of any anti‐hormone manipulation. CONCLUSIONS Erlotinib efficacy was higher in androgen‐sensitive PCa cells when we compare to the effects evident in CRPC cells, whereas the carnertinib efficacy may have therapeutical significance in Her2 overexpressing AR+ CRPC models in combination with hormone manipulation. Prostate 71:1481–1491, 2011. © 2011 Wiley‐Liss, Inc.