Data · study · 2026
Anti-Notch plus endocrine therapy in ER+ breast cancer inhibits cancer stem cells by increasing DAXX
Listed in NCBI GEO
Resistance to endocrine therapy (ET) in ER+ breast cancer is mediated by Notch signaling, but the clinical application of anti-Notch therapy has been limited by the lack of predictive biomarkers.
Description
To identify Notch-regulated biomarkers, we conducted a pre-surgical window study evaluating ET combined with the γ-secretase inhibitor (GSI) MK-0752. RNA expressions in tumors were measured using an Affymetrix array and by real-time PCR.
ET plus GSI showed more genes were decreased than ET alone. Specifically, DAXX, NOXA, and LFNG RNAs were increased, while fifteen additional transcripts were decreased. Mechanistically, GSI reduced Notch1 occupancy at CSL-binding elements within HES1, HEY2, HEYL, CCND1, MKI67, and DAXX genes, and inhibited cancer stem cells (CSCs) by 90–100%.
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This anti-CSC effect required DAXX, while GSI treatment or Notch1/4 knockdown increased DAXX expression, suggesting transcriptional repression by Notch. Using mouse tumor xenograft studies, ET plus MK-0752 resulted in complete regression of MCF-7 tumors, with DAXX-high tumors showing greater treatment sensitivity. Clinically, high DAXX expression was associated with improved recurrence-free and overall survival.
This study found that anti-Notch plus ET in ER+ breast cancer inhibits cancer stem cells by increasing DAXX, a promising predictive biomarker. These findings support clinical evaluation of therapies that increase DAXX expression.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE342nnn/GSE342234 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE342234 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1506811 ncbi.nlm.nih.gov/bioproject/PRJNA1506811 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by array · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Cancer 75%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE342234 | 7 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:cancer | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-array | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:9606 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |