ArticleScientific reports2020
Combination treatment with a PI3K/Akt/mTOR pathway inhibitor overcomes resistance to anti-HER2 therapy in PIK3CA-mutant HER2-positive breast cancer cells.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 85 citations in OpenAlex.
- AKT Phosphorylation of FOXK2 at Ser398 Impacts Breast Cancer Cell Growth and Viability.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- HER2 targeted therapy resistance in breast cancer: from molecular landscape to clinical aspects.Science China. Life sciences · 2026Review
- Capivasertib Combines with Trastuzumab Deruxtecan to Enhance Antitumor Activity in HER2-Positive and HER2-Low Tumors.Molecular cancer therapeutics · 2026Article
- 17-DMAG-Loaded HER2-Targeted Extracellular Vesicles Induce PARP/Caspase3-Mediated Apoptosis in Gastric Carcinoma.International journal of molecular sciences · 2026Article
- The impact of the PI3K/AKT/mTOR signaling pathway on trastuzumab resistance in HER2-positive gastric cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Article
- Neoantigen Targeting as a Novel Approach for Therapy-Resistant Tumors.Molecular diagnosis & therapy · 2026Review
- Tumor mutations predict HER2-targeted therapy resistance in primary HER2-positive breast cancer.NPJ breast cancer · 2026Article
- Transcriptional modulation of the PI3K/AKT/mTOR signaling pathway mediated by HPV16Exploration of targeted anti-tumor therapy · 2026Article
- The prognostic impact of human epidermal growth factor receptor 2 status in metastatic colorectal cancer.Future science OA · 2025Article
- Article
- Clinical and Morphological Features of ER-Positive HER2-Negative Breast Tumors with PIK3CA Mutations in Russian Patients.Cancers · 2025Article
- PARP inhibitors elicit a cellular senescence mediated inflammatory response in homologous recombination proficient cancer cells.Scientific reports · 2025Article
- Signaling pathway dysregulation in breast cancer.Oncotarget · 2025Review
- CD36 inhibition enhances the anti-proliferative effects of PI3K inhibitors in PTEN-loss anti-HER2 resistant breast cancer cells.Cancer & metabolism · 2025Article
- Therapeutic challenges in HER2-targeted antibody therapies: trastuzumab and its ADC derivatives in breast cancer.American journal of cancer research · 2025Review
- High frequency of the PIK3CA H1047L mutation in Indonesian breast cancer across molecular subtypes.PloS one · 2025Article
- Predictive significance ofFrontiers in oncology · 2025Article
- PPARG Activation of Fatty Acid Metabolism Drives Resistance to Anti-HER2 Therapies in HER2-Positive Breast Cancer.International journal of biological sciences · 2025Article
- The Biological Roles and Clinical Applications of the PI3K/AKT Pathway in Targeted Therapy Resistance in HER2-Positive Breast Cancer: A Comprehensive Review.International journal of molecular sciences · 2024Review
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Amplification and/or overexpression of human epidermal growth factor receptor 2 (HER2) are observed in 15-20% of breast cancers (HER2+ breast cancers), and anti-HER2 therapies have significantly improved prognosis of patients with HER2+ breast cancer. One resistance mechanism to anti-HER2 therapies is constitutive activation of the phosphoinositide 3-kinase (PI3K) pathway. Combination therapy with small-molecule inhibitors of AKT and HER2 was conducted in HER2+ breast cancer cell lines with or without PIK3CA mutations, which lead to constitutive activation of the PI3K pathway. PIK3CA mutations played important roles in resistance to single-agent anti-HER2 therapy in breast cancer cell lines. Combination therapy of a HER2 inhibitor and an AKT inhibitor, as well as other PI3K pathway inhibitors, could overcome the therapeutic limitations associated with single-agent anti-HER2 treatment in PIK3CA-mutant HER2+ breast cancer cell lines. Furthermore, expression of phosphorylated 4E-binding protein 1 (p4EBP1) following the treatment correlated with the antiproliferative activities of the combination, suggesting that p4EBP1 may have potential as a prognostic and/or efficacy-linking biomarkers for these combination therapies in patients with HER2+ breast cancer. These findings highlight potential clinical strategies using combination therapy to overcome the limitations associated with single-agent anti-HER2 therapies in patients with HER2+ breast cancer.
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