ArticleCancer research2009
PIK3CA and PIK3CB inhibition produce synthetic lethality when combined with estrogen deprivation in estrogen receptor-positive breast cancer.
Article in Cancer research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers, 4 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
95 citing papers in PubMed, 4 syntheses or guidelines pooled it, 228 citations in OpenAlex.
- Pooled it
- Genetic alterations of histone lysine methyltransferases and their significance in breast cancer.Oncotarget · 2015Pooled it
- Prognostic role of PIK3CA mutations and their association with hormone receptor expression in breast cancer: a meta-analysis.Scientific reports · 2014Pooled it
- A meta-analysis of multiple matched copy number and transcriptomics data sets for inferring gene regulatory relationships.PloS one · 2014Pooled it
- 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
- Trial
- A Phase II Trial of Neoadjuvant MK-2206, an AKT Inhibitor, with Anastrozole in Clinical Stage II or IIIClinical cancer research : an official journal of the American Association for Cancer Research · 2017Trial
- NeoPalAna: Neoadjuvant Palbociclib, a Cyclin-Dependent Kinase 4/6 Inhibitor, and Anastrozole for Clinical Stage 2 or 3 Estrogen Receptor-Positive Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Trial
- Phase II Randomized Preoperative Window-of-Opportunity Study of the PI3K Inhibitor Pictilisib Plus Anastrozole Compared With Anastrozole Alone in Patients With Estrogen Receptor-Positive Breast Cancer.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2016Trial
- LYN-activating mutations mediate antiestrogen resistance in estrogen receptor-positive breast cancer.The Journal of clinical investigation · 2014Trial
- Therapeutic advances in HR+/HER2- advanced breast cancer after failure of CDK4/6 inhibitor therapy.Frontiers in oncology · 2026Review
- PI3K Signaling at the Crossroads of Lipid Metabolism and Cancer.Advances in experimental medicine and biology · 2025Review
- Targeted Therapies and Drug Resistance in Advanced Breast Cancer, Alternative Strategies and the Way beyond.Cancers · 2024Review
- Brain metastasis in breast cancer: focus on genes and signaling pathways involved, blood-brain barrier and treatment strategies.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Review
- PI3K-AKT-Targeting Breast Cancer Treatments: Natural Products and Synthetic Compounds.Biomolecules · 2023Review
- Review
- Promising Therapeutic Impact of a Selective Estrogen Receptor Downregulator, Fulvestrant, as Demonstrated In Vitro upon Low-Grade Serous Ovarian Carcinoma Cell Lines.Current oncology (Toronto, Ont.) · 2022Article
- Targeting AKT in ER-Positive HER2-Negative Metastatic Breast Cancer: From Molecular Promises to Real Life Pitfalls?International journal of molecular sciences · 2021Review
- PI3Kinase Inhibition in Hormone Receptor-Positive Breast Cancer.International journal of molecular sciences · 2021Review
- Review
35 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
Several phosphoinositide 3-kinase (PI3K) catalytic subunit inhibitors are currently in clinical trial. We therefore sought to examine relationships between pharmacologic inhibition and somatic mutations in PI3K catalytic subunits in estrogen receptor (ER)-positive breast cancer, in which these mutations are particularly common. RNA interference (RNAi) was used to determine the effect of selective inhibition of PI3K catalytic subunits, p110alpha and p110beta, in ER(+) breast cancer cells harboring either mutation (PIK3CA) or gene amplification (PIK3CB). p110alpha RNAi inhibited growth and promoted apoptosis in all tested ER(+) breast cancer cells under estrogen deprived-conditions, whereas p110beta RNAi only affected cells harboring PIK3CB amplification. Moreover, dual p110alpha/p110beta inhibition potentiated these effects. In addition, treatment with the clinical-grade PI3K catalytic subunit inhibitor BEZ235 also promoted apoptosis in ER(+) breast cancer cells. Importantly, estradiol suppressed apoptosis induced by both gene knockdowns and BEZ235 treatment. Our results suggest that PI3K inhibitors should target both p110alpha and p110beta catalytic subunits, whether wild-type or mutant, and be combined with endocrine therapy for maximal efficacy when treating ER(+) breast cancer.
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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.