ArticleCancer cell2015
Measurement of PIP3 levels reveals an unexpected role for p110β in early adaptive responses to p110α-specific inhibitors in luminal breast cancer.
Article in Cancer cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 123 papers, 1 of them a synthesis that pooled it.
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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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
123 citing papers in PubMed, 1 synthesis or guideline pooled it, 214 citations in OpenAlex.
- The prognostic value of PI3K mutational status in breast cancer: A meta-analysis.Journal of cellular biochemistry · 2018Pooled it
- Phase II Study of Copanlisib in Patients With PTEN Loss: Results From NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocols Z1G and Z1H.JCO precision oncology · 2025Trial
- A renaissance in targeting the PI3K/AKT/mTOR pathway.Nature reviews. Drug discovery · 2026Review
- Effect of PI3K-p110α Inhibitor Alpelisib in the Differentiation and Effector Functions of M-CSF and GM-CSF Macrophages.International journal of molecular sciences · 2026Article
- Approaches to visualize, quantify, and manipulate phosphoinositides in cells.Histochemistry and cell biology · 2026Review
- Targeting FGFR signaling overcomes therapeutic resistance and immune evasion in oncogenic PIK3CA-driven serous-like endometrial cancer.Nature communications · 2026Article
- Design, Synthesis, and Biological Evaluation of Novel Triazine-Based Dual Histone Deacetylase/phosphatidylinositol 3-kinase Inhibitors for Breast Cancer Therapy.ChemMedChem · 2026Article
- Cooperative Roles of Class IA PI3K Isoforms in Translocation-Related Sarcoma Cell Survival and Proliferation.Cancer research communications · 2026Article
- The role of the striatin family proteins in hippo signaling and cellular regulation.Cell & bioscience · 2025Article
- Downregulation of PIP4K2C inhibits the breast cancer cell proliferation, migration and invasion.Translational oncology · 2025Article
- Review
- Use of metabolic imaging to monitor heterogeneity of tumour response following therapeutic mTORC1/2 pathway inhibition.Disease models & mechanisms · 2025Article
- Exploring the antiproliferative effect of PI3K/Akt/mTOR pathway and CDK4/6 inhibitors in human papillomavirus‑positive and ‑negative head and neck squamous cell carcinoma cell lines.International journal of oncology · 2025Article
- Oral Estrogen Receptor PROTAC Vepdegestrant (ARV-471) Is Highly Efficacious as Monotherapy and in Combination with CDK4/6 or PI3K/mTOR Pathway Inhibitors in Preclinical ER+ Breast Cancer Models.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Resistance to Targeted Inhibitors of the PI3K/AKT/mTOR Pathway in Advanced Oestrogen-Receptor-Positive Breast Cancer.Cancers · 2024Review
- Cell-Permeable Fluorescent Sensors Enable Rapid Live Cell Visualization of Plasma Membrane and Nuclear PIP3 Pools.JACS Au · 2024Article
- A novel pan-PI3K inhibitor KTC1101 synergizes with anti-PD-1 therapy by targeting tumor suppression and immune activation.Molecular cancer · 2024Article
- Integrative modeling uncovers p21-driven drug resistance and prioritizes therapies for PIK3CA-mutant breast cancer.NPJ precision oncology · 2024Article
- The mechanisms of class 1A PI3K and Wnt/β-catenin coupled signaling in breast cancer.Biochemical Society transactions · 2023Review
- PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer.Molecular cancer · 2023Review
63 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
BYL719, which selectively inhibits the alpha isoform of the phosphatidylinositol 3-kinase (PI3K) catalytic subunit (p110a), is currently in clinical trials for the treatment of solid tumors, especially luminal breast cancers with PIK3CA mutations and/or HER2 amplification. This study reveals that, even among these sensitive cancers, the initial efficacy of p110α inhibition is mitigated by rapid re-accumulation of the PI3K product PIP3 produced by the p110β isoform. Importantly, the reactivation of PI3K mediated by p110β does not invariably restore AKT phosphorylation, demonstrating the limitations of using phospho-AKT as a surrogate to measure PI3K activation. Consistently, we show that the addition of the p110β inhibitor to BYL719 prevents the PIP3 rebound and induces greater antitumor efficacy in HER2-amplified and PIK3CA mutant cancers.
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What OpenQuestion holds
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.