ArticleScience translational medicine2015
PI3K inhibition results in enhanced estrogen receptor function and dependence in hormone receptor-positive breast cancer.
Article in Science translational medicine, 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 201 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.
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Who cites it
201 citing papers in PubMed, 434 citations in OpenAlex.
- Very low-carbohydrate ketogenic diet in treatment-naïve women with endometrial cancer and overweight: a randomized feasibility study.Nature communications · 2026Trial
- Capivasertib plus fulvestrant in patients with HR-positive/HER2-negative advanced breast cancer: phase 3 CAPItello-291 study extended Chinese cohort.Nature communications · 2025Trial
- Capivasertib in Hormone Receptor-Positive Advanced Breast Cancer.The New England journal of medicine · 2023Trial
- Ipatasertib plus paclitaxel for PIK3CA/AKT1/PTEN-altered hormone receptor-positive HER2-negative advanced breast cancer: primary results from cohort B of the IPATunity130 randomized phase 3 trial.Breast cancer research and treatment · 2022Trial
- Phase III randomized study of taselisib or placebo with fulvestrant in estrogen receptor-positive, PIK3CA-mutant, HER2-negative, advanced breast cancer: the SANDPIPER trial.Annals of oncology : official journal of the European Society for Medical Oncology · 2021Trial
- Everolimus plus exemestane in hormone-receptor-positive, HER2-negative locally advanced or metastatic breast cancer: incidence and time course of adverse events in the phase IIIb BALLET population.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2020Trial
- Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive breast cancer (FAKTION): a multicentre, randomised, controlled, phase 2 trial.The Lancet. Oncology · 2020Trial
- Oral metronomic vinorelbine combined with endocrine therapy in hormone receptor-positive HER2-negative breast cancer: SOLTI-1501 VENTANA window of opportunity trial.Breast cancer research : BCR · 2019Trial
- A Phase II Randomized Study of Neoadjuvant Letrozole Plus Alpelisib for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer (NEO-ORB).Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Trial
- BEECH: a dose-finding run-in followed by a randomised phase II study assessing the efficacy of AKT inhibitor capivasertib (AZD5363) combined with paclitaxel in patients with estrogen receptor-positive advanced or metastatic breast cancer, and in a PIK3CA mutant sub-population.Annals of oncology : official journal of the European Society for Medical Oncology · 2019Trial
- Phase II Study of Taselisib (GDC-0032) in Combination with Fulvestrant in Patients with HER2-Negative, Hormone Receptor-Positive Advanced Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Trial
- Phase I Dose-Escalation Study of Taselisib, an Oral PI3K Inhibitor, in Patients with Advanced Solid Tumors.Cancer discovery · 2017Trial
- Buparlisib plus fulvestrant versus placebo plus fulvestrant in postmenopausal, hormone receptor-positive, HER2-negative, advanced breast cancer (BELLE-2): a randomised, double-blind, placebo-controlled, phase 3 trial.The Lancet. Oncology · 2017Trial
- PI3K signaling in breast cancer: therapeutic advances versus adaptive resistance.The Journal of clinical investigation · 2026Review
- Regulation of oestrogen signalling by the receptor tyrosine kinase cKIT stabilises Barrett's oesophagus pre-malignant state.Biology open · 2026Article
- Insulin receptor substrate 2 (IRS2) confers resistance to PI3K pathway inhibition in PIK3CA mutant breast cancer.The Journal of biological chemistry · 2026Article
- Exon 7 splicing of ERα predicts poor prognosis and increases phenotypic heterogeneity in luminal a subtype breast cancer.FEBS open bio · 2026Article
- Multiple programmed cell death patterns predict the prognosis and therapeutic sensitivity in head and neck squamous cell carcinoma.Discover oncology · 2026Article
- Deciphering molecular pathways in urological cancers: A gateway to precision therapeutics.Journal of advanced research · 2026Review
- Construction of an Adverse Outcome Pathway Framework for Glyphosate-Induced Female Reproductive Toxicity Based on Toxicity Pathways.Environment & health (Washington, D.C.) · 2026Review
141 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
28 authors at 3 institutions in 1 country.
Funding
Abstract
Activating mutations of PIK3CA are the most frequent genomic alterations in estrogen receptor (ER)-positive breast tumors, and selective phosphatidylinositol 3-kinase α (PI3Kα) inhibitors are in clinical development. The activity of these agents, however, is not homogeneous, and only a fraction of patients bearing PIK3CA-mutant ER-positive tumors benefit from single-agent administration. Searching for mechanisms of resistance, we observed that suppression of PI3K signaling results in induction of ER-dependent transcriptional activity, as demonstrated by changes in expression of genes containing ER-binding sites and increased occupancy by the ER of promoter regions of up-regulated genes. Furthermore, expression of ESR1 mRNA and ER protein were also increased upon PI3K inhibition. These changes in gene expression were confirmed in vivo in xenografts and patient-derived models and in tumors from patients undergoing treatment with the PI3Kα inhibitor BYL719. The observed effects on transcription were enhanced by the addition of estradiol and suppressed by the anti-ER therapies fulvestrant and tamoxifen. Fulvestrant markedly sensitized ER-positive tumors to PI3Kα inhibition, resulting in major tumor regressions in vivo. We propose that increased ER transcriptional activity may be a reactive mechanism that limits the activity of PI3K inhibitors and that combined PI3K and ER inhibition is a rational approach to target these tumors.
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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.