ArticleGynecologic oncology2017
Superior in vitro and in vivo activity of trastuzumab-emtansine (T-DM1) in comparison to trastuzumab, pertuzumab and their combination in epithelial ovarian carcinoma with high HER2/neu expression.
Article in Gynecologic oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Combined inhibition of HER2 and VEGFR synergistically improves therapeutic efficacy via PI3K-AKT pathway in advanced ovarian cancer.Journal of experimental & clinical cancer research : CR · 2024Article
- HER2-targeted therapies in cancer: a systematic review.Biomarker research · 2024Review
- The Poly (ADP-ribose) polymerase inhibitor olaparib and pan-ErbB inhibitor neratinib are highly synergistic in HER2 overexpressing epithelial ovarian carcinoma in vitro and in vivo.Gynecologic oncology · 2023Article
- Ado-tratuzumab emtansine beyond breast cancer: therapeutic role of targeting other HER2-positive cancers.Frontiers in molecular biosciences · 2023Review
- Focusing on NK cells and ADCC: A promising immunotherapy approach in targeted therapy for HER2-positive breast cancer.Frontiers in immunology · 2022Review
- A HER2 Tri-Specific NK Cell Engager Mediates Efficient Targeting of Human Ovarian Cancer.Cancers · 2021Article
- Enhancement of tumor tropism of mPEGylated nanoparticles by anti-mPEG bispecific antibody for ovarian cancer therapy.Scientific reports · 2021Article
- Novel antibody-drug conjugates: current and future roles in gynecologic oncology.Current opinion in obstetrics & gynecology · 2021Review
- Integrative network analysis identifies potential targets and drugs for ovarian cancer.BMC medical genomics · 2020Article
- Two engineered site-specific antibody-drug conjugates, HLmD4 and HLvM4, have potent therapeutic activity in two DLL4-positive tumour xenograft models.American journal of cancer research · 2020Article
- Human epidermal growth factor receptor targeted inhibitors for the treatment of ovarian cancer.Cancer biology & medicine · 2018Article
- Inhibition of BET Bromodomain Proteins with GS-5829 and GS-626510 in Uterine Serous Carcinoma, a Biologically Aggressive Variant of Endometrial Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- A stage IV high-grade serous ovarian cancer patient carryingScience progressArticle
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Authors and funding
22 authors at 1 institution in 1 country.
Funding
Abstract
backgroundEpithelial ovarian cancer (EOC) remains the most lethal gynecologic malignancy. The objective of this study was to compare the anti-tumor activity of HER2/neu-targeting monoclonal antibodies, trastuzumab (T), pertuzumab (P), combination of trastuzumab and pertuzumab (T+P) and trastuzumab-emtansine (T-DM1) in EOC with high HER2/neu expression.
methodsPrimary EOC cell lines were established and cell blocks were analyzed for HER2/neu expression. Cytostatic, apoptotic and antibody-dependent cell-mediated cytotoxicity (ADCC) activities of T, P, T+P and T-DM1 were evaluated in vitro. The in vivo antitumor activity was tested in xenograft models with 3+ HER2/neu expression.
resultsHigh (3+) HER2/neu expression was detected in 40% of the primary EOC cell lines. T, P, T+P, and T-DM1 were similarly effective in inducing strong ADCC against primary EOC cell lines expressing 3+ HER2/neu. The combination of T and P was more cytostatic when compared with that of T or P used alone (p<0.0001 and p<0.0001, respectively). T-DM1 induced significantly more apoptosis when compared with T+P (p<0.0001). Finally, T-DM1 was significantly more effective in tumor growth inhibition in vivo in EOC xenografts overexpressing HER2/neu when compared to T alone, P alone and T+P (p=0.04).
conclusionIn vitro and in vivo experiments with 3+ HER2/neu expressing EOC revealed limited anti-tumor activity of T or P. T-DM1 showed superior anti-tumor activity to T and P as single agents and as a combination. Our preclinical data support the design of clinical studies with T-DM1 for the treatment of chemotherapy-resistant EOC overexpressing HER2/neu.
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