ArticleBMC cancer2016
Integrated molecular pathway analysis informs a synergistic combination therapy targeting PTEN/PI3K and EGFR pathways for basal-like breast cancer.
Article in BMC cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis 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
19 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Everolimus in Advanced Breast Cancer: A Systematic Review and Meta-analysis.Targeted oncology · 2020Pooled it
- Article
- EGFR amplification and PI3K pathway mutations identify a subset of breast cancers that synergistically respond to EGFR and PI3K inhibition.bioRxiv : the preprint server for biology · 2025Article
- EB1089 Increases the Antiproliferative Response of Lapatinib in Combination with Antiestrogens in HER2-Positive Breast Cancer Cells.International journal of molecular sciences · 2024Article
- Synthesis and Biological Evaluation of (Pharmaceuticals (Basel, Switzerland) · 2021Article
- NVP-BEZ235 or JAKi Treatment leads to decreased survival of examined GBM and BBC cells.Cancer treatment and research communications · 2021Article
- The mutational landscape of the SCAN-B real-world primary breast cancer transcriptome.EMBO molecular medicine · 2020Article
- Combined targeting of G protein-coupled receptor and EGF receptor signaling overcomes resistance to PI3K pathway inhibitors in PTEN-null triple negative breast cancer.EMBO molecular medicine · 2020Article
- Stathmin expression associates with vascular and immune responses in aggressive breast cancer subgroups.Scientific reports · 2020Article
- Multi-targeted kinase inhibition alleviates mTOR inhibitor resistance in triple-negative breast cancer.Breast cancer research and treatment · 2019Article
- Prioritization of metabolic genes as novel therapeutic targets in estrogen-receptor negative breast tumors using multi-omics data and text mining.Oncotarget · 2019Article
- PI3Kα Pathway Inhibition With Doxorubicin Treatment Results in Distinct Biventricular Atrophy and Remodeling With Right Ventricular Dysfunction.Journal of the American Heart Association · 2019Article
- Prognositic significance of P-cadherin expression in breast cancer: Protocol for a meta-analysis.Medicine · 2019Article
- Epidermal Growth Factor Reverses the Inhibitory Effects of the Bisphosphonate, Zoledronic Acid, on Human Oral Keratinocytes and Human Vascular Endothelial Cells In Vitro via the Epidermal Growth Factor Receptor (EGFR)/Akt/Phosphoinositide 3-Kinase (PI3K) Signaling Pathway.Medical science monitor : international medical journal of experimental and clinical research · 2019Article
- Article
- Inhibition of basal-like breast cancer growth by FTY720 in combination with epidermal growth factor receptor kinase blockade.Breast cancer research : BCR · 2017Article
- Interaction of glycosphingolipids GD3 and GD2 with growth factor receptors maintains breast cancer stem cell phenotype.Oncotarget · 2017Article
- A molecular pathway analysis stresses the role of inflammation and oxidative stress towards cognition in schizophrenia.Journal of neural transmission (Vienna, Austria : 1996) · 2017Article
- Recent advances in the use of PI3K inhibitors for glioblastoma multiforme: current preclinical and clinical development.Molecular cancer · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors.
Funding
Abstract
backgroundThe basal-like breast cancer (BLBC) subtype is characterized by positive staining for basal mammary epithelial cytokeratin markers, lack of hormone receptor and HER2 expression, and poor prognosis with currently no approved molecularly-targeted therapies. The oncogenic signaling pathways driving basal-like tumorigenesis are not fully elucidated.
methodsOne hundred sixteen unselected breast tumors were subjected to integrated analysis of phosphoinositide 3-kinase (PI3K) pathway related molecular aberrations by immunohistochemistry, mutation analysis, and gene expression profiling. Incidence and relationships between molecular biomarkers were characterized. Findings for select biomarkers were validated in an independent series. Synergistic cell killing in vitro and in vivo tumor therapy was investigated in breast cancer cell lines and mouse xenograft models, respectively.
resultsSixty-four % of cases had an oncogenic alteration to PIK3CA, PTEN, or INPP4B; when including upstream kinases HER2 and EGFR, 75 % of cases had one or more aberration including 97 % of estrogen receptor (ER)-negative tumors. PTEN-loss was significantly associated to stathmin and EGFR overexpression, positivity for the BLBC markers cytokeratin 5/14, and the BLBC molecular subtype by gene expression profiling, informing a potential therapeutic combination targeting these pathways in BLBC. Combination treatment of BLBC cell lines with the EGFR-inhibitor gefitinib plus the PI3K pathway inhibitor LY294002 was synergistic, and correspondingly, in an in vivo BLBC xenograft mouse model, gefitinib plus PI3K-inhibitor PWT-458 was more effective than either monotherapy and caused tumor regression.
conclusionsOur study emphasizes the importance of PI3K/PTEN pathway activity in ER-negative and basal-like breast cancer and supports the future clinical evaluation of combining EGFR and PI3K pathway inhibitors for the treatment of BLBC.
Indexed as
Identifiers
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.