Improving glioblastoma chemotherapy with gene therapy to reduce drug resistance

Inhibition of the DNA repair protein MGMT in glioblastoma cells may enhance the effectiveness of temozolomide chemotherapy.

• MGMT overexpression is associated with reduced effectiveness of temozolomide in glioblastoma treatment.
• Lentiviral delivery of anti-MGMT small hairpin RNA (shRNA) resulted in specific inhibition of MGMT expression in GBM cell lines and subcutaneous tumors.
• Xenografts with low MGMT expression showed tumor growth inhibition following temozolomide treatment, unlike those with high MGMT expression.
• Bioluminescence imaging confirmed efficient transduction of GBM xenografts with lentiviruses expressing luciferase and shRNA.
• Combination treatment of anti-MGMT shRNA and temozolomide reduced tumor size, while control shRNA with temozolomide did not.

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