ArticleBritish journal of cancer2014
Afatinib demonstrates remarkable activity against HER2-amplified uterine serous endometrial cancer in vitro and in vivo.
Article in British journal of cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02491099 (A Phase II Evaluation of Afatanib, an Irreversible Human Epidermal Growth Factor Receptor 2), which is not on this map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
A Phase II Evaluation of Afatanib, an Irreversible Human Epidermal Growth Factor Receptor 2 (Her2/Neu) Tyrosine Kinase Inhibitor, in Patients With Persistent or Recurrent HER2-positive Uterine Serous Carcinoma
Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Functional impact of the hyperduplication genomophenotype in high copy number endometrial cancer.iScience · 2025Article
- Narrative review on the evolving role of HER2/neu targeting in uterine serous cancers.Annals of translational medicine · 2024Review
- The Evaluation of Drugs as Potential Modulators of the Trafficking and Maturation of ACE2, the SARS-CoV-2 Receptor.Biomolecules · 2024Article
- HER2 Oncogene as Molecular Target in Uterine Serous Carcinoma and Uterine Carcinosarcoma.Cancers · 2023Review
- Targeting receptor tyrosine kinases in ovarian cancer: Genomic dysregulation, clinical evaluation of inhibitors, and potential for combinatorial therapies.Molecular therapy oncolytics · 2023Review
- Human epidermal growth factor receptor 2 targeted therapy in endometrial cancer: Clinical and pathological perspectives.World journal of clinical oncology · 2021Review
- Ethacrynic Acid Enhances the Antitumor Effects of Afatinib in EGFR/T790M-Mutated NSCLC by Inhibiting WNT/Beta-Catenin Pathway Activation.Disease markers · 2021Article
- Antibody-Targeted Imaging of Gastric Cancer.Molecules (Basel, Switzerland) · 2020Review
- Human epidermal growth factor 2 (HER2) in early stage uterine serous carcinoma: A multi-institutional cohort study.Gynecologic oncology · 2020Article
- Article
- Targeting human epidermal growth factor receptor 2 (HER2) in gynecologic malignancies.Current opinion in obstetrics & gynecology · 2020Review
- PI3K oncogenic mutations mediate resistance to afatinib in HER2/neu overexpressing gynecological cancers.Gynecologic oncology · 2019Article
- Efficacy of afatinib in aOncoTargets and therapy · 2019Article
- Phase I dose-escalation trial of afatinib, an irreversible ErbB family blocker, in combination with gemcitabine or docetaxel in patients with relapsed or refractory solid tumors.Investigational new drugs · 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
- Targeted Therapies in Type II Endometrial Cancers: Too Little, but Not Too Late.International journal of molecular sciences · 2018Review
- Dual HER2/PIK3CA Targeting Overcomes Single-Agent Acquired Resistance in HER2-Amplified Uterine Serous Carcinoma Cell Lines In Vitro and In Vivo.Molecular cancer therapeutics · 2015Article
- PIK3CA oncogenic mutations represent a major mechanism of resistance to trastuzumab in HER2/neu overexpressing uterine serous carcinomas.British journal of cancer · 2015Article
- Dacomitinib (PF-00299804), a second-generation irreversible pan-erbB receptor tyrosine kinase inhibitor, demonstrates remarkable activity against HER2-amplified uterine serous endometrial cancer in vitro.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundUterine serous carcinomas (USCs) are an aggressive form of uterine cancer that may rely on HER2/neu amplification as a driver of proliferation. The objective of this paper is to assess the sensitivity of USC cell lines with and without HER2/neu gene amplification to afatinib, an irreversible ErbB tyrosine kinase inhibitor, and to test the efficacy of afatinib in the treatment of HER2-amplified USC xenografts.
methodsEight of fifteen primary USC cell lines (four with HER2 amplification and four without) demonstrating similar in vitro growth rates were treated with scalar concentrations of afatinib. Effects on cell growth, signalling and cell cycle distribution were determined by flow cytometry assays. Mice harbouring xenografts of HER2/neu-amplified USC were treated with afatinib by gavage to determine the effect on tumour growth and overall survival.
resultsPrimary chemotherapy-resistant USC cell lines harbouring HER2/neu gene amplification were exquisitely sensitive to afatinib exposure (mean ± s.e.m. IC50=0.0056 ± 0.0006 μM) and significantly more sensitive than HER2/neu-non-amplified USC cell lines (mean ± s.e.m. IC50=0.563 ± 0.092 μM, P<0.0001). Afatinib exposure resulted in abrogation of cell survival, inhibition of HER2/neu autophosphorylation and S6 transcription factor phosphorylation in HER2/neu overexpressing USC and inhibited the growth of HER2-amplified tumour xenografts improving overall survival (P=0.0017).
conclusionsAfatinib may be highly effective against HER2/neu-amplified chemotherapy-resistant USC. The investigation of afatinib in patients harbouring HER2/neu-amplified USC is warranted.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.