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.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (12)
Humeyra Kaanoglu
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine
Yasemin K. Akyel
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine
Adebimpe Adefolaju
Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina
Alain Valdivia
Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina
Dominique Higgins
Department of Neurosurgery, University of North Carolina
Rani S. Sellers
Department of Pathology and Laboratory Medicine, University of North Carolina
Caroline Mosely
UNC Advanced Translational Pharmacology and Analytical Chemistry Laboratory, UNC Eshelman School of Pharmacy, University of North Carolina
Corey J. Haswell
UNC Advanced Translational Pharmacology and Analytical Chemistry Laboratory, UNC Eshelman School of Pharmacy, University of North Carolina
William C. Zamboni
UNC Advanced Translational Pharmacology and Analytical Chemistry Laboratory, UNC Eshelman School of Pharmacy, University of North Carolina
Shawn D. Hingtgen
Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina
Andrew B. Satterlee
Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina
Aziz Sancar