ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014
Dual HER2 targeting impedes growth of HER2 gene-amplified uterine serous carcinoma xenografts.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 41 citations in OpenAlex.
- Quantifying HER-2 for Precision Oncology: The Role of Optical Biosensors.Molecular biotechnology · 2026Review
- Targeting FGFR signaling overcomes therapeutic resistance and immune evasion in oncogenic PIK3CA-driven serous-like endometrial cancer.Nature communications · 2026Article
- Genomic Landscape of ctDNA and Real-World Outcomes in Advanced Endometrial Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- HER2-Positive Serous Endometrial Cancer Treatment: Current Clinical Practice and Future Directions.Medicina (Kaunas, Lithuania) · 2024Review
- Review
- High-Grade Endometrial Cancer: Molecular Subtypes, Current Challenges, and Treatment Options.Reproductive sciences (Thousand Oaks, Calif.) · 2024Review
- Narrative review on the evolving role of HER2/neu targeting in uterine serous cancers.Annals of translational medicine · 2024Review
- Targeting Galectin 3 illuminates its contributions to the pathology of uterine serous carcinoma.British journal of cancer · 2024Article
- Sialyl-Tn serves as a potential therapeutic target for ovarian cancer.Journal of ovarian research · 2024Article
- Consistency between Primary Uterine Corpus Malignancies and Their Corresponding Patient-Derived Xenograft Models.International journal of molecular sciences · 2024Article
- A review of basic to clinical targeted therapy and immunotherapy in uterine serous cancer.Molecular biology reports · 2023Review
- Review
- Patient-Derived Xenograft Models for Endometrial Cancer Research.International journal of molecular sciences · 2018Review
- Targeted Therapies in Type II Endometrial Cancers: Too Little, but Not Too Late.International journal of molecular sciences · 2018Review
- MicroRNA 21a-5p overexpression impacts mediators of extracellular matrix formation in uterine leiomyoma.Reproductive biology and endocrinology : RB&E · 2018Article
- Treatment of ovarian cancer by targeting the tumor stem cell-associated carbohydrate antigen, Sialyl-Thomsen-nouveau.Oncotarget · 2018Article
- The allosteric AKT inhibitor, MK2206, decreases tumor growth and invasion in patient derived xenografts of endometrial cancer.Cancer biology & therapy · 2017Article
- The Therapeutic Challenge of Targeting HER2 in Endometrial Cancer.The oncologist · 2015Review
- HER2 over-expressing high grade endometrial cancer expresses high levels of p95HER2 variant.Gynecologic oncology · 2015Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
purposeUterine serous carcinoma (USC) is an aggressive subtype of endometrial cancer that commonly harbors HER2 gene amplification. We investigated the effectiveness of HER2 inhibition using lapatinib and trastuzumab in vitro and in xenografts derived from USC cell lines and USC patient-derived xenografts. EXPERIMENTAL
designImmunohistochemistry and FISH were performed to assess HER2 expression in 42 primary USC specimens. ARK1, ARK2, and SPEC2 cell lines were treated with trastuzumab or lapatinib. Cohorts of mice harboring xenografts derived from ARK2 and SPEC2 cell lines and EnCa1 and EnCa2 primary human USC samples were treated with either vehicle, trastuzumab, lapatinib, or the combination of trastuzumab and lapatinib. Acute and chronic posttreatment tumor samples were assessed for downstream signaling alterations and examined for apoptosis and proliferation.
resultsHER2 gene amplification (24%) correlated significantly with HER2 protein overexpression (55%). All models were impervious to single-agent trastuzumab treatment. Lapatinib decreased in vitro proliferation of all cell lines and in vivo growth of HER2-amplified xenografts (ARK2, EnCa1). In addition, dual therapy with trastuzumab and lapatinib resulted in significant antitumor activity only in ARK2 and EnCa1 tumors. Dual HER2 therapy induced on target alteration of downstream MAPK and PI3K pathway mediators only in HER2-amplified models, and was associated with increased apoptosis and decreased proliferation.
conclusionsAlthough trastuzumab alone did not impact USC growth, dual anti-HER2 therapy with lapatinib led to improved inhibition of tumor growth in HER2-amplified USC and may be a promising avenue for future investigation.
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Registered trials
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