title: Antitumor effects of carnertinib in castration resistant prostate cancer models: a comparative study with erlotinib.
abstract: OBJECTIVE
  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.
  
  
  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.
authors: Division 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.
authors: Giovanni Luca
authors: GL
authors: Gravina
authors: Francesco
authors: F
authors: Marampon
authors: Margherita
authors: M
authors: Piccolella
authors: Leda
authors: L
authors: Biordi
authors: Corrado
authors: C
authors: Ficorella
authors: Marcella
authors: M
authors: Motta
authors: Emmanuele A
authors: EA
authors: Jannini
authors: Vincenzo
authors: V
authors: Tombolini
authors: Claudio
authors: C
authors: Festuccia
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D019008:Drug Resistance, Neoplasm; D004847:Epithelial Cells / Q000166:cytology; D000069347:Erlotinib Hydrochloride; D006801:Humans; D008297:Male; D008819:Mice, Nude; D009025:Morpholines / Q000494:pharmacology*; D009570:Nitriles / Q000494:pharmacology; D009919:Orchiectomy; D011467:Prostate / Q000166:cytology*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology*; D014105:Tosyl Compounds / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000726:Androgen Antagonists; D000813:Anilides; D009025:Morpholines; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D014105:Tosyl Compounds; C053541:bicalutamide; C420268:Canertinib; D000069347:Erlotinib Hydrochloride