Gene Therapy for Gliomas

The overall median survival in glioblastoma multiforme (GBM) patients is less than one year and fewer than 5% of patients survive more than 5 years. The current standard of care for GBM patients involves neurosurgical resection of the tumor followed by radiotherapy with concomitant and adjuvant temozolomide chemotherapy. After initial treatment, all malignant gliomas eventually recur, mostly within a 2-3 cm margin of the original tumor on CT/MRI. The poor prognosis warrants research into new treatment modalities for malignant gliomas. Novel therapeutic approaches in the treatment of GBM include chemotherapy, targeted molecular agents, immunotherapy and virotherapy/gene therapy. Because malignant gliomas only rarely metastasize outside the skull, novel locoregional treatment modalities such as gene therapy are potentially interesting. The aim of this thesis was to identify bottlenecks limiting the efficacy of glioma gene therapy and address some of these bottlenecks in the laboratory.