ArticleBritish journal of cancer2015
PIK3CA oncogenic mutations represent a major mechanism of resistance to trastuzumab in HER2/neu overexpressing uterine serous carcinomas.
Article in British journal of cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 40 citations in OpenAlex.
- DHX9 Inhibition Enhances Paclitaxel Sensitivity by Inducing Mitotic Failure in Ovarian and Endometrial Cancers.Molecular cancer therapeutics · 2026Article
- AXL inhibition improves the therapeutic efficacy of trastuzumab in high-risk endometrial cancer.Gynecologic oncology · 2026Article
- Review
- Narrative review on the evolving role of HER2/neu targeting in uterine serous cancers.Annals of translational medicine · 2024Review
- In Vivo and In Vitro Efficacy of Trastuzumab Deruxtecan in Uterine Serous Carcinoma.Molecular cancer therapeutics · 2023Article
- HER2 Genetic Intratumor Heterogeneity Is Associated With Resistance to Trastuzumab and Trastuzumab Emtansine Therapy in Recurrent High-Grade Endometrial Cancer.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2023Article
- The Current Status and Future Perspectives of Chimeric Antigen Receptor-Engineered T Cell Therapy for the Management of Patients with Endometrial Cancer.Current issues in molecular biology · 2023Review
- Histopathologic features and molecular genetic landscape of HER2-amplified endometrial carcinomas.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2022Article
- Article
- Review
- Gene expression profiling identified TP53Oncology letters · 2020Article
- Somatic mutation profiling inAmerican journal of cancer research · 2020Article
- PI3K oncogenic mutations mediate resistance to afatinib in HER2/neu overexpressing gynecological cancers.Gynecologic oncology · 2019Article
- Silencing theYonsei medical journal · 2019Article
- Efficacy of afatinib in aOncoTargets and therapy · 2019Article
- Monoclonal antibody therapy of solid tumors: clinical limitations and novel strategies to enhance treatment efficacy.Biologics : targets & therapy · 2019Review
- PP2A: A Promising Biomarker and Therapeutic Target in Endometrial Cancer.Frontiers in oncology · 2019Review
- 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
- Article
Corrections and comments
- Erratum issued
Authors and funding
15 authors at 1 institution in 2 countries.
Funding
Abstract
objectivesWe evaluated the role of PIK3CA-mutations as mechanism of resistance to trastuzumab in primary HER2/neu-amplified uterine-serous-carcinoma (USC) cell lines.
methodsFifteen whole-exome-sequenced USC cell lines were tested for HER2/neu-amplification and PIK3CA-mutations. Four HER2/neu-amplified USC (2-harbouring wild-type-PIK3CA-genes and 2-harbouring oncogenic-PIK3CA-mutations) were evaluated in in vitro dose-titration-proliferation-assays, cell-viability and HER2 and S6-protein-phosphorylation after exposure to trastuzumab. USC harbouring wild-type-PIK3CA were transfected with plasmids encoding oncogenic PIK3CA-mutations (i.e., H1047R/R93Q) and exposed to trastuzumab. Finally, trastuzumab efficacy was tested by using two USC xenograft mouse models.
resultsSeven out of fifteen (46%) of the USC cell lines were HER2/neu-amplified by fluorescence in situ hybridisation. Within these tumours four out of seven (57%) were found to harbour oncogenic PIK3CA-mutations vs two out of eight (25%) of the HER2/neu not amplified cell lines (P=0.01). HER2/neu-amplified/PIK3CA-mutated USC were highly resistant to trastuzumab when compared with HER2/neu-amplified/wild-type-PIK3CA cell lines (P=0.02). HER2/neu-amplified/PIK3CA wild-type cell lines transfected with oncogenic PIK3CA-mutations increased their resistance to trastuzumab (P<0.0001). Trastuzumab was effective in reducing tumour growth (P=0.001) and improved survival (P=0.0001) in mouse xenografts harbouring HER2-amplified/PIK3CA wild-type USC but not in HER2-amplified/PIK3CA-mutated tumours.
conclusionsOncogenic PIK3CA mutations are common in HER2/neu-amplified USC and may constitute a major mechanism of resistance to trastuzumab treatment.
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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.