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Updated: Mar 7, 2026
Bioluminescence Imaging of an Immunocompetent Animal Model for Glioblastoma
Published on: January 15, 2016
Targeting Protein Kinase CK2: Evaluating CX-4945 Potential for GL261 Glioblastoma Therapy in Immunocompetent Mice
Laura Ferrer-Font1,2,3, Lucia Villamañan4, Nuria Arias-Ramos5,6
1Departament de Bioquímica i Biologia Molecular, Unitat de Bioquímica de Biociències, Edifici C, Universitat Autònoma de Barcelona, Cerdanyola del Vallès 08193, Spain. Laura.Ferrer@uab.cat.
Abstract:
Glioblastoma (GBM) causes poor survival in patients even with aggressive treatment. Temozolomide (TMZ) is the standard chemotherapeutic choice for GBM treatment but resistance always ensues. Protein kinase CK2 (CK2) contributes to tumour development and proliferation in cancer, and it is overexpressed in human GBM. Accordingly, targeting CK2 in GBM may benefit patients. Our goal has been to evaluate whether CK2 inhibitors (iCK2s) could increase survival in an immunocompetent preclinical GBM model. Cultured GL261 cells were treated with different iCK2s including CX-4945, and target effects evaluated in vitro. CX-4945 was found to decrease CK2 activity and Akt(S129) phosphorylation in GL261 cells. Longitudinal in vivo studies with CX-4945 alone or in combination with TMZ were performed in tumour-bearing mice. Increase in survival (p < 0.05) was found with combined CX-4945 and TMZ metronomic treatment (54.7 ± 11.9 days, n = 6) when compared to individual metronomic treatments (CX-4945: 24.5 ± 2.0 and TMZ: 38.7 ± 2.7, n = 6) and controls (22.5 ± 1.2, n = 6). Despite this, CX-4945 did not improve mice outcome when administered on every/alternate days, either alone or in combination with 3-cycle TMZ. The highest survival rate was obtained with the metronomic combined TMZ+CX-4945 every 6 days, pointing to the participation of the immune system or other ancillary mechanism in therapy response.
Insights
Combining the protein kinase CK2 inhibitor CX-4945 with temozolomide (TMZ) chemotherapy significantly extended survival in a preclinical glioblastoma model. Metronomic administration every six days showed the greatest survival benefit, suggesting immune system involvement.
Area of Science:
- Oncology
- Pharmacology
- Immunology
Background:
- Glioblastoma (GBM) is an aggressive brain tumor with poor patient survival, often developing resistance to standard chemotherapy like temozolomide (TMZ).
- Protein kinase CK2 (CK2) is overexpressed in GBM and promotes tumor growth, making it a potential therapeutic target.
Purpose of the Study:
- To evaluate the efficacy of CK2 inhibitors (iCK2s) in increasing survival in an immunocompetent preclinical GBM model.
- To determine if combining CX-4945 with TMZ improves survival outcomes in GBM-bearing mice.
Main Methods:
- GL261 glioblastoma cells were treated in vitro with CX-4945 to assess its effects on CK2 activity and Akt phosphorylation.
- In vivo studies involved administering CX-4945 alone or in combination with TMZ using different schedules (metronomic, every/alternate days) in tumor-bearing mice.
- Survival rates were compared between treatment groups and controls.
Main Results:
- CX-4945 effectively reduced CK2 activity and Akt phosphorylation in GL261 cells.
- Metronomic combination therapy with CX-4945 and TMZ administered every six days significantly increased median survival (54.7 days) compared to individual treatments or controls (22.5-38.7 days).
- CX-4945 alone or with TMZ did not improve survival when given on every/alternate days.
Conclusions:
- Metronomic combination therapy of CX-4945 and TMZ demonstrates significant survival benefits in a preclinical GBM model.
- The optimal efficacy was observed with metronomic administration every six days, suggesting a role for immune system or other mechanisms in treatment response.
- Targeting CK2 with inhibitors like CX-4945 warrants further investigation as a potential adjuvant therapy for glioblastoma.
