ArticleMolecular cancer therapeutics2015
Dual HER2/PIK3CA Targeting Overcomes Single-Agent Acquired Resistance in HER2-Amplified Uterine Serous Carcinoma Cell Lines In Vitro and In Vivo.
Article in Molecular cancer therapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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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.
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Who cites it
27 citing papers in PubMed, 37 citations in OpenAlex.
- Molecular Pathways and Biomarkers in Endometrial Carcinoma: Paving the Way for Precision Medicine.Anti-cancer agents in medicinal chemistry · 2026Review
- Review
- HER2-Positive Serous Endometrial Cancer Treatment: Current Clinical Practice and Future Directions.Medicina (Kaunas, Lithuania) · 2024Review
- 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
- Article
- HER2 Oncogene as Molecular Target in Uterine Serous Carcinoma and Uterine Carcinosarcoma.Cancers · 2023Review
- Critical Overview of Serous Endometrial Intraepithelial Cancer Treatment: Systematic Review of Adjuvant Options.Life (Basel, Switzerland) · 2023Review
- ErbB3-Targeting Oncolytic Adenovirus Causes Potent Tumor Suppression by Induction of Apoptosis in Cancer Cells.International journal of molecular sciences · 2022Article
- The Prognostic Role and Significance of Dll4 and Toll-like Receptors in Cancer Development.Cancers · 2022Review
- Human epidermal growth factor receptor 2 targeted therapy in endometrial cancer: Clinical and pathological perspectives.World journal of clinical oncology · 2021Review
- Uterine serous carcinoma.Gynecologic oncology · 2021Review
- Review
- Phase II evaluation of copanlisib, a selective inhibitor of Pi3kca, in patients with persistent or recurrent endometrial carcinoma harboring PIK3CA hotspot mutations: An NRG Oncology study (NRG-GY008).Gynecologic oncology reports · 2020Article
- 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
- PP2A: A Promising Biomarker and Therapeutic Target in Endometrial Cancer.Frontiers in oncology · 2019Review
- Targeted Therapies in Type II Endometrial Cancers: Too Little, but Not Too Late.International journal of molecular sciences · 2018Review
- Targeting ERBB2 mutations in solid tumors: biological and clinical implications.Journal of hematology & oncology · 2018Article
- Evaluation of the HER/PI3K/AKT Family Signaling Network as a Predictive Biomarker of Pathologic Complete Response for Patients With Breast Cancer Treated With Neratinib in the I-SPY 2 TRIAL.JCO precision oncology · 2018Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 2 countries.
Funding
Abstract
HER2/neu gene amplification and PIK3CA driver mutations are common in uterine serous carcinoma (USC) and may represent ideal therapeutic targets against this aggressive variant of endometrial cancer. We examined the sensitivity to neratinib, taselisib, and the combination of the two compounds in in vitro and in vivo experiments using PIK3CA-mutated and PIK3CA wild-type HER2/neu-amplified USC cell lines. Cell viability and cell-cycle distribution were assessed using flow-cytometry assays. Downstream signaling was assessed by immunoblotting. Preclinical efficacy of single versus dual inhibition was evaluated in vivo using two USC xenografts. We found both single-agent neratinib and taselisib to be active but only transiently effective in controlling the in vivo growth of USC xenografts harboring HER2/neu gene amplification with or without oncogenic PIK3CA mutations. In contrast, the combination of the two inhibitors caused a stronger and long-lasting growth inhibition in both USC xenografts when compared with single-agent therapy. Combined targeting of HER2 and PIK3CA was associated with a significant and dose-dependent increase in the percentage of cells in the G0-G1 phase of the cell cycle and a dose-dependent decline in the phosphorylation of S6. Importantly, dual inhibition therapy initiated after tumor progression in single-agent-treated mice was still remarkably effective at inducing tumor regression in both large PIK3CA and pan-ErbB inhibitor-resistant USC xenografts. Dual HER2/PIK3CA blockade may represent a novel therapeutic option for USC patients harboring tumors with HER2/neu gene amplification and mutated or wild-type PIK3CA resistant to chemotherapy.
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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.