Related Experiment Video
Updated: Jun 3, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Antitumor effects of carnertinib in castration resistant prostate cancer models: a comparative study with erlotinib
Giovanni Luca Gravina1, Francesco Marampon, Margherita Piccolella
1Division of Radiotherapy, Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy; Department of Experimental Medicine, Radiobiology Laboratory, University of L'Aquila, L'Aquila, Italy.
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.
Insights
Carnertinib shows promise for treating Her2-positive castration-resistant prostate cancer (CRPC) when combined with hormone therapy. Erlotinib was less effective in CRPC models compared to hormone-sensitive prostate cancer.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Preclinical studies suggested EGFR and HER2 inhibition for castration-resistant prostate cancer (CRPC).
- However, clinical trials with these inhibitors have not shown significant benefit in CRPC patients.
- This study investigates two inhibitors, erlotinib (EGFR-specific) and carnertinib (pan-erbB), in prostate cancer models.
Purpose of the Study:
- To compare the efficacy of erlotinib and carnertinib in hormone-sensitive and castration-resistant prostate cancer (CRPC) cell lines.
- To evaluate the in vitro and in vivo effects of these inhibitors on cancer cell proliferation, cell cycle, and apoptosis.
- To assess the potential of carnertinib in combination therapies for CRPC.
Main Methods:
- In vitro assessment of proliferation, cell cycle, and apoptosis following erlotinib and carnertinib treatment.
- In vivo studies using 22rv1 (AR-expressing) and PC3 (AR-negative) CRPC xenograft models in nude mice.
- Combination therapy experiments involving bicalutamide (BCLT) and anti-target agents in 22rv1 models.
Main Results:
- Erlotinib and carnertinib efficacy correlated with HER2 expression and activation levels.
- Erlotinib's effectiveness was dependent on the EGFR/HER2 ratio, favoring higher EGFR levels.
- Carnertinib demonstrated superior in vitro efficacy compared to erlotinib and showed activity with anti-hormone manipulation, unlike erlotinib combinations.
Conclusions:
- Erlotinib showed greater efficacy in androgen-sensitive prostate cancer cells than in CRPC cells.
- Carnertinib may hold therapeutic potential for HER2-overexpressing AR+ CRPC models, particularly when combined with hormone manipulation.
