Efficacy of neratinib in the treatment of HER2/neu-amplified epithelial ovarian carcinoma in vitro and in vivo

• Published in: Medical oncology (Northwood, London, England) London, England), 2017-05, Vol.34 (5), p.91-91, Article 91
• Main Authors: Menderes, Gulden, Bonazzoli, Elena, Bellone, Stefania, Black, Jonathan D., Lopez, Salvatore, Pettinella, Francesca, Masserdotti, Alice, Zammataro, Luca, Litkouhi, Babak, Ratner, Elena, Silasi, Dan-Arin, Azodi, Masoud, Schwartz, Peter E., Santin, Alessandro D.
• Format: Article
• Language: English
• Subjects: Aged; Animals; Carcinoma, Ovarian Epithelial; Cell Cycle - drug effects; Cell Line, Tumor; Cell Survival - drug effects; Drug Screening Assays, Antitumor; Female; Gene Amplification; Hematology; Humans; Internal Medicine; Medicine; Medicine & Public Health; Mice; Middle Aged; Neoplasms, Glandular and Epithelial - drug therapy; Neoplasms, Glandular and Epithelial - enzymology; Neoplasms, Glandular and Epithelial - genetics; Neoplasms, Glandular and Epithelial - pathology; Oncology; Original Paper; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - enzymology; Ovarian Neoplasms - genetics; Ovarian Neoplasms - pathology; Pathology; Quinolines - pharmacology; Receptor, ErbB-2 - antagonists & inhibitors; Receptor, ErbB-2 - biosynthesis; Receptor, ErbB-2 - genetics; Signal Transduction; Xenograft Model Antitumor Assays
• ISSN: 1357-0560; 1559-131X
• DOI: 10.1007/s12032-017-0956-8

Epithelial ovarian carcinoma is the most lethal of gynecologic malignancies. There is a need to optimize the currently available treatment strategies and to urgently develop novel therapeutic agents against chemotherapy-resistant disease. The objective of our study was to evaluate neratinib’s preclinical efficacy in treating HER2-amplified ovarian cancer. Neratinib’s efficacy in treating HER2-amplified ovarian cancer was studied in vitro utilizing six primary tumor cell lines with differential HER2/neu expression. Flow cytometry was utilized to assess IC 50 , cell signaling changes, and cell cycle distribution. Neratinib’s in vivo efficacy was evaluated in HER2-amplified epithelial ovarian carcinoma xenografts. Three of six (50%) ovarian cancer cell lines were HER2/neu-amplified. Neratinib showed significantly higher efficacy in treating HER2/neu-amplified cell lines when compared to the non-HER2/neu-amplified tumor cell lines (mean ± SEM IC 50 :0.010 μM ± 0.0003 vs. 0.076 μM ± 0.005 p