ArticleOncogene2016
PI3K-p110α mediates resistance to HER2-targeted therapy in HER2+, PTEN-deficient breast cancers.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 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.
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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
33 citing papers in PubMed, 42 citations in OpenAlex.
- HER2 targeted therapy resistance in breast cancer: from molecular landscape to clinical aspects.Science China. Life sciences · 2026Review
- The role of genetics and epigenetics in breast cancer: A comprehensive review of metastasis, risk factors, and future perspectives.Journal of pharmaceutical analysis · 2025Review
- Progress and prospects of biomarker-based targeted therapy and immune checkpoint inhibitors in advanced gastric cancer.Frontiers in oncology · 2024Review
- Inhibition of PI3K Signaling Intensified the Antileukemic Effects of Pioglitazone: New Insight into the Application of PPARγ Stimulators in Acute Lymphoblastic Leukemia.Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2023Article
- Article
- Signaling pathways and therapeutic interventions in gastric cancer.Signal transduction and targeted therapy · 2022Review
- Review
- Review
- Inhibiting ERK5 overcomes breast cancer resistance to anti-HER2 therapy by targeting the G1/S cell cycle transition.Cancer research communications · 2022Article
- Review
- CDK4/6 inhibitors: a brief overview and prospective research directions.RSC advances · 2021Review
- Understanding and overcoming tumor heterogeneity in metastatic breast cancer treatment.Nature cancer · 2021Review
- Long Noncoding RNA GAS5 in Breast Cancer: Epigenetic Mechanisms and Biological Functions.International journal of molecular sciences · 2021Review
- The role of HER2 and HER3 in HER2-amplified cancers beyond breast cancers.Scientific reports · 2021Article
- The changing treatment of metastatic her2-positive breast cancer.Oncology letters · 2021Review
- Activation of PI3K/AKT/mTOR Pathway Causes Drug Resistance in Breast Cancer.Frontiers in pharmacology · 2021Review
- Genomic landscape of metastatic breast cancer identifies preferentially dysregulated pathways and targets.The Journal of clinical investigation · 2020Article
- Lipid metabolic reprogramming as an emerging mechanism of resistance to kinase inhibitors in breast cancer.Cancer drug resistance (Alhambra, Calif.) · 2020Article
- Inhibition of the transcriptional kinase CDK7 overcomes therapeutic resistance in HER2-positive breast cancers.Oncogene · 2020Article
- PI3Kα Pathway Inhibition With Doxorubicin Treatment Results in Distinct Biventricular Atrophy and Remodeling With Right Ventricular Dysfunction.Journal of the American Heart Association · 2019Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Human epidermal growth factor receptor-2 (HER2) amplification/overexpression (HER2+) frequently co-occurs with PI3K pathway activation in breast tumors. PI3K signaling is most often activated by PIK3CA mutation or PTEN loss, which frequently results in sensitivity to p110α or p110β inhibitors, respectively. To examine the p110 isoform dependence in HER2+, PTEN-deficient tumors, we generated genetic mouse models of breast tumors driven by concurrent Her2 activation and Pten loss coupled with deletion of p110α or p110β. Ablation of p110α, but not p110β, significantly impaired the development of Her2+/Pten-null tumors in mice. We further show that p110α primarily mediates oncogenic signaling in HER2+/PTEN-deficient human cancers while p110β conditionally mediates PI3K/AKT signaling only upon HER2 inhibition. Combined HER2 and p110α inhibition effectively reduced PI3K/AKT signaling and growth of cancer cells both in vitro and in vivo. Addition of the p110β inhibitor to dual HER2 and p110α inhibition induced tumor regression in a xenograft model of HER2+/PTEN-deficient human cancers. Together, our data suggest that combined inhibition of HER2 and p110α/β may serve as a potent and durable therapeutic regimen for the treatment of HER2+, PTEN-deficient breast tumors.
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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.