Omics · study · 2026
Combined dopamine receptor inhibition and radiotherapy target mesothelioma-initiating cells and increase survival in a mouse model of mesothelioma [scRNA-Seq]
Listed in NCBI GEO
Malignant pleural mesothelioma (MPM) is a rare thoracic cancer associated with poor prognosis and low survival rates.
Description
In solid cancers, repurposed dopamine receptor antagonists have been shown to have anti-cancer effects. Moreover, in combination with radiotherapy, quetiapine (QTP), a dopamine (D) 2/3 receptor antagonist, has been shown to interfere with self-renewal capacity in glioma-initiating cells and increase survival in mouse models of glioblastoma.
In this study we explore combined treatment effects in MPM. Using mesothelioma cell lines, MSTO-211H, H2052, and H2452, and MSTO-211H-derived orthotopic xenograft mouse model of MPM we examined how QTP combined with radiation affects mesothelioma-initiating cells (MICs) in vitro and survival in vivo. Subsequently, bulk and single cell RNA sequencing was used to characterize the transcriptomic landscape of MSTO-211H treated with combined radiation and QTP.
Read the rest (2 more)
We demonstrate that combining QTP with radiation reduces MIC self-renewal capacity and stem cell frequency. In vivo, this combination therapy significantly extends the median survival of mesothelioma-bearing mice. Clonogenic survival assays revealed that QTP does not enhance radiosensitivity in the tested mesothelioma cell lines.
Sequencing data revealed, combined treatment upregulated genes involved in cholesterol homeostasis, depleted cancer stem cells, and increased cellular senescence. Taken together, our study highlights the therapeutic potential of radiation with QTP in the treatment of MPM.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE326nnn/GSE326484 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE326484 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1445686 ncbi.nlm.nih.gov/bioproject/PRJNA1445686 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Cancer 75% · RNA sequencing 75% · Sequencing 75% · Single-cell RNA sequencing 65%
Provenance · 1 source records, 11 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE326484 | 12 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-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[modality].local:modality:sequencing | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[modality].local:modality:single-cell-rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| 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 |