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. (C) 2011 Wiley-Liss, Inc.

Antitumor effects of carnertinib in castration resistant prostate cancer models: A Comparative study with erlotinib / Giovanni Luca Gravina, ; Marampon, Francesco; Margherita, Piccolella; Leda, Biordi; Corrado, Ficorella; Marcella, Motta; Jannini, Emmanuele A.; Tombolini, Vincenzo; Claudio, Festuccia. - In: THE PROSTATE. - ISSN 0270-4137. - STAMPA. - 71:14(2011), pp. 1481-1491. ((Intervento presentato al convegno XXXV National Congress of the italian society of endocrinology tenutosi a Montesilvano nel 18-21 maggio 2011 [10.1002/pros.21363].

Antitumor effects of carnertinib in castration resistant prostate cancer models: A Comparative study with erlotinib.

Francesco Marampon;TOMBOLINI, Vincenzo;
2011

Abstract

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. (C) 2011 Wiley-Liss, Inc.
bicalutamide; castrated resistant prostate cancer; epidermal growth factor receptors; erlotinib and carnertinib
01 Pubblicazione su rivista::01a Articolo in rivista
Antitumor effects of carnertinib in castration resistant prostate cancer models: A Comparative study with erlotinib / Giovanni Luca Gravina, ; Marampon, Francesco; Margherita, Piccolella; Leda, Biordi; Corrado, Ficorella; Marcella, Motta; Jannini, Emmanuele A.; Tombolini, Vincenzo; Claudio, Festuccia. - In: THE PROSTATE. - ISSN 0270-4137. - STAMPA. - 71:14(2011), pp. 1481-1491. ((Intervento presentato al convegno XXXV National Congress of the italian society of endocrinology tenutosi a Montesilvano nel 18-21 maggio 2011 [10.1002/pros.21363].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/378686
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