Discovery of a Therapeutic Agent for Glioblastoma Using a Systems Biology-Based Drug Repositioning Approach.
Int J Mol Sci
; 25(14)2024 Jul 18.
Article
in En
| MEDLINE
| ID: mdl-39063109
ABSTRACT
Glioblastoma (GBM), a highly malignant tumour of the central nervous system, presents with a dire prognosis and low survival rates. The heterogeneous and recurrent nature of GBM renders current treatments relatively ineffective. In our study, we utilized an integrative systems biology approach to uncover the molecular mechanisms driving GBM progression and identify viable therapeutic drug targets for developing more effective GBM treatment strategies. Our integrative analysis revealed an elevated expression of CHST2 in GBM tumours, designating it as an unfavourable prognostic gene in GBM, as supported by data from two independent GBM cohorts. Further, we pinpointed WZ-4002 as a potential drug candidate to modulate CHST2 through computational drug repositioning. WZ-4002 directly targeted EGFR (ERBB1) and ERBB2, affecting their dimerization and influencing the activity of adjacent genes, including CHST2. We validated our findings by treating U-138 MG cells with WZ-4002, observing a decrease in CHST2 protein levels and a reduction in cell viability. In summary, our research suggests that the WZ-4002 drug candidate may effectively modulate CHST2 and adjacent genes, offering a promising avenue for developing efficient treatment strategies for GBM patients.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Glioblastoma
/
Systems Biology
/
Drug Repositioning
Limits:
Humans
Language:
En
Journal:
Int J Mol Sci
Year:
2024
Document type:
Article
Country of publication:
Suiza