ArticleGynecologic oncology2019
PI3K oncogenic mutations mediate resistance to afatinib in HER2/neu overexpressing gynecological cancers.
Article in Gynecologic oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- Diagnostic and therapeutic advances for HER2-expressing or amplified gynecologic cancers.Gynecologic oncology · 2025Review
- Review
- Unveiling the Molecular Mechanism of Trastuzumab Resistance in SKBR3 and BT474 Cell Lines for HER2 Positive Breast Cancer.Current issues in molecular biology · 2024Article
- Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies.Signal transduction and targeted therapy · 2023Review
- Engineering Bifunctional Calcium Alendronate Gene-Delivery Nanoneedle for Synergistic Chemo/Immuno-Therapy Against HER2 Positive Ovarian Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- The Prognostic Role and Significance of Dll4 and Toll-like Receptors in Cancer Development.Cancers · 2022Review
- Ipatasertib, an oral AKT inhibitor, inhibits cell proliferation and migration, and induces apoptosis in serous endometrial cancer.American journal of cancer research · 2022Article
- Uterine serous carcinoma.Gynecologic oncology · 2021Review
- Recent Research Progress of Chiral Small Molecular Antitumor-Targeted Drugs Approved by the FDA From 2011 to 2019.Frontiers in oncology · 2021Review
- Erb‑B2 Receptor Tyrosine Kinase 2 is negatively regulated by the p53‑responsive microRNA‑3184‑5p in cervical cancer cells.Oncology reports · 2021Observational
- Derangements in HUWE1/c-MYC pathway confer sensitivity to the BET bromodomain inhibitor GS-626510 in uterine cervical carcinoma.Gynecologic oncology · 2020Article
- PIK3CA gene aberrancy and role in targeted therapy of solid malignancies.Cancer gene therapy · 2020Review
- Design and syntheses of 7-nitro-2-aryl-4Journal of molecular structure · 2020Article
- Review
Corrections and comments
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Authors and funding
24 authors at 2 institutions in 2 countries.
Funding
Abstract
objectiveAberrant expression of HER2/neu and PIK3CA gene products secondary to amplification/mutations are common in high-grade-serous-endometrial (USC) and ovarian-cancers (HGSOC). Because scant information is currently available in the literature on the potential negative effect of PIK3CA mutations on the activity of afatinib, in this study we evaluate for the first time the role of oncogenic PIK3CA mutations as a potential mechanism of resistance to afatinib in HGSOC and USC overexpressing HER2/neu.
methodsWe used six whole-exome-sequenced primary HGSOC/USC cell-lines and three xenografts overexpressing HER2/neu and harboring mutated or wild-type PIK3CA/PIK3R1 genes to evaluate the role of PI3K-mutations as potential mechanism of resistance to afatinib, an FDA-approved pan-c-erb-inhibitor in clinical trials in USC. Primary-USC harboring wild-type-PIK3CA gene was transfected with plasmids encoding oncogenic PIK3CA-mutations (H1047R/E545K). The effect of afatinib on HER2/PI3K/AKT/mTOR pathway was evaluated by immunoblotting.
resultsWe found PI3K wild-type cell-lines to be significantly more sensitive (lower IC
conclusionsOncogenic PI3K mutations may represent a major mechanism of resistance to afatinib. Combinations of c-erb with PIK3CA, AKT or mTOR inhibitors may be necessary to more efficiently block the PIK3CA/AKT/mTOR pathway.
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