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Culture Dimensionality Modulates Gallium Maltolate Response in Glioblastoma: Comparative Analyses in 2D and 3D
Paulina Szeliska1, Karol Jaroch1, Weronika Wróblewska1
1Department of Pharmacodynamics and Molecular Pharmacology, Faculty of Pharmacy, Collegium Medicum, Nicolaus Copernicus University, Jurasza 2, 85-089 Bydgoszcz, Poland.
Molecular Pharmaceutics
|January 16, 2026
Summary
Gallium maltolate (GaM) effectively reduced glioblastoma (GBM) cell viability across various models. However, 3D culture impacts drug response variably, highlighting the need for diverse models to predict GaM efficacy.
Area of Science:
- Oncology
- Pharmacology
- Biochemistry
Background:
- Glioblastoma (GBM) is an aggressive brain tumor with limited treatment options.
- Gallium maltolate (GaM) is an investigational drug targeting iron-dependent processes in cancer cells.
- Response to GaM varies, necessitating a deeper understanding of its efficacy across different GBM contexts.
Purpose of the Study:
- To evaluate the efficacy of Gallium maltolate (GaM) in diverse glioblastoma (GBM) models.
- To investigate the influence of 2D versus 3D culture systems on GaM response.
- To identify predictive biomarkers for GaM sensitivity in GBM.
Main Methods:
- Utilized established and patient-derived GBM cell lines in 2D and 3D cultures.
- Assessed cell viability using IC10, IC50, and IC90 modeling.
- Quantified transferrin receptor (TFRC) expression and measured oxygen consumption rate (OCR).
- Performed multivariate metabolomic analyses (PCA/PLS-DA) to identify metabolic signatures.
Main Results:
- GaM reduced viability in all GBM models, with 3D culture showing line-specific effects on drug resistance.
- Transferrin receptor (TFRC) levels correlated with IC50 in 2D but not 3D, suggesting other factors influence response in 3D.
- Metabolomic analysis revealed a signature of tryptophan, methionine, uracil, and allantoin perturbations, indicating impacts on amino acid, nucleotide, and redox pathways.
Conclusions:
- Complementary 2D and 3D patient-derived GBM models are crucial for mechanistic studies and predicting GaM response.
- A broader phenotype beyond TFRC, including TFRC/CD44/MGMT and TFR2 expression, is associated with 3D sensitization or protection.
- The study provides insights into GaM's mechanism of action and identifies potential biomarkers for treatment selection in GBM.
