Combinatorial treatment of glioblastoma with temozolomide (TMZ) plus 5-ethynyl-2'-deoxyuridine (EdU).

Abstract

Glioblastoma (GBM) is the most aggressive malignant primary brain tumor in adults, with incidence peaking in later life. It is commonly treated with surgery followed by administration of ionizing radiation and the DNA-alkylating agent temozolomide (TMZ). Even though this regimen confers some progression-free survival, there is essentially no cure with the median survival with the standard of care being about 12 mo. Currently, several alternative approaches are being developed to improve upon this outcome. We have already shown EdU alone effectively treats GBM, and we now study the efficacy of TMZ+EdU combination therapy. TMZ+EdU significantly improves antitumor efficacy compared to either single-agent therapy against GBM cell lines in vitro, against three different orthotopic GBM xenograft models, and against passage-zero GBM patient tumor tissues engrafted within an organotypic brain slice culture-based platform. Together, our results suggest that EdU could be effective alongside standard-of-care TMZ in patients with GBM.