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Title:
Efficacy of neratinib in the treatment of HER2/neu-amplified epithelial ovarian carcinoma in vitro and in vivo | Medical Oncology
Description:
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 neratinibās preclinical efficacy in treating HER2-amplified ovarian cancer. Neratinibās 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 IC50, cell signaling changes, and cell cycle distribution. Neratinibās 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 IC50:0.010 μM ± 0.0003 vs. 0.076 μM ± 0.005 p < 0.0001). Neratinib treatment significantly decreased the phosphorylation of the transcription factor S6, leading to arrest of the cell cycle in G0/G1 phase. Neratinib prolonged survival in mice harboring HER2-amplified epithelial ovarian carcinoma xenografts (p = 0.003). Neratinib inhibits proliferation, signaling, cell cycle progression and tumor growth of HER2-amplified epithelial ovarian carcinoma in vitro. Neratinib inhibits xenograft growth and improves overall survival in HER2/neu-amplified ovarian cancer in vivo. Clinical trials are warranted.
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Keywords {š}
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Topics {āļø}
biomarker triplet nampt/vegf/her2 her2/neu-amplified ovarian cancer month download article/chapter erbb family-targeted agents her2-positive breast cancer hr-/her2+ breast cancer university campus bio-medico differential her2/neu expression trastuzumab-based adjuvant therapy endometrial serous carcinoma u01 ca176067-01a1 grants her2/neu receptor de la garza-salazar ovarian carcinoma tissue her2/neu-amplified epithelial ovarian cancers her2-directed therapy anti-her2 therapy short-term survivors 2-positive breast cancer her2 amplified carcinosarcoma full article pdf metastatic breast cancer recurrent ovarian cancer early breast cancer clinical trials siegel er capecitabine combination therapy human breast cancer privacy choices/manage cookies ovarian carcinoma transcription factor s6 cell cycle progression related subjects c-erbb-2 oncoprotein her2 therapy 2/neu gene amplification g0/g1 phase breast cancer res standard her2 testing nat rev cancer cancer treat rev schwab cl targeted therapies somatic brca1/2 mutations human participants performed article menderes neratinib inhibits proliferation irreversible inhibitor ovarian cancer
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headline:Efficacy of neratinib in the treatment of HER2/neu-amplified epithelial ovarian carcinoma in vitro and in vivo
description: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 neratinibās preclinical efficacy in treating HER2-amplified ovarian cancer. Neratinibās 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 IC50, cell signaling changes, and cell cycle distribution. Neratinibās 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 IC50:0.010 μM ± 0.0003 vs. 0.076 μM ± 0.005 pĀ <Ā 0.0001). Neratinib treatment significantly decreased the phosphorylation of the transcription factor S6, leading to arrest of the cell cycle in G0/G1 phase. Neratinib prolonged survival in mice harboring HER2-amplified epithelial ovarian carcinoma xenografts (pĀ =Ā 0.003). Neratinib inhibits proliferation, signaling, cell cycle progression and tumor growth of HER2-amplified epithelial ovarian carcinoma in vitro. Neratinib inhibits xenograft growth and improves overall survival in HER2/neu-amplified ovarian cancer in vivo. Clinical trials are warranted.
datePublished:2017-04-10T00:00:00Z
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Epithelial ovarian carcinoma
SCID mice
HER2/neu
Oncology
Hematology
Pathology
Internal Medicine
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headline:Efficacy of neratinib in the treatment of HER2/neu-amplified epithelial ovarian carcinoma in vitro and in vivo
description: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 neratinibās preclinical efficacy in treating HER2-amplified ovarian cancer. Neratinibās 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 IC50, cell signaling changes, and cell cycle distribution. Neratinibās 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 IC50:0.010 μM ± 0.0003 vs. 0.076 μM ± 0.005 pĀ <Ā 0.0001). Neratinib treatment significantly decreased the phosphorylation of the transcription factor S6, leading to arrest of the cell cycle in G0/G1 phase. Neratinib prolonged survival in mice harboring HER2-amplified epithelial ovarian carcinoma xenografts (pĀ =Ā 0.003). Neratinib inhibits proliferation, signaling, cell cycle progression and tumor growth of HER2-amplified epithelial ovarian carcinoma in vitro. Neratinib inhibits xenograft growth and improves overall survival in HER2/neu-amplified ovarian cancer in vivo. Clinical trials are warranted.
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Epithelial ovarian carcinoma
SCID mice
HER2/neu
Oncology
Hematology
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