Researchers at the University of North Carolina (UNC) School of Medicine and the UNC Eshelman School of Pharmacy have reported a significant development in glioblastoma treatment. Their study, published in Proceedings of the National Academy of Sciences, found that combining temozolomide (TMZ), a standard chemotherapy drug, with EdU, a commonly used laboratory chemical, led to notable survival rates and cancer remission in preclinical models.
"We did a number of preclinical studies: Some with EdU alone, some with TMZ alone, and others with both together," said Nobel laureate Aziz Sancar, MD, PhD, biochemist and member of UNC Lineberger Comprehensive Cancer Center. "The concept is simple. When we combined TMZ with EdU, we found that the two drugs acting together can destroy these tumors and prevent death."
Glioblastoma is an aggressive brain cancer with limited treatment options. Current therapies have remained largely unchanged for two decades. Only about 7% of patients survive more than five years after diagnosis. Temozolomide remains the only FDA-approved chemotherapy for this condition but often fails to prevent tumor recurrence.
Sancar's team discovered that EdU could enter brain tissue and selectively kill tumor cells without harming healthy tissue. This prompted further investigation into using EdU alongside TMZ as a combination therapy.
In their experiments on mouse models implanted with human glioblastoma cell lines (U87 and GBM8), researchers observed complete cancer reduction when both drugs were administered together. Mice treated with the combination survived beyond 250 days in one model and remained tumor-free after 170 days in another.
Toxicity tests showed only mild and reversible side effects affecting organs such as the small intestine and spleen—findings consistent with typical chemotherapy reactions.
The study also revealed what Sancar described as a "synergistic effect" between TMZ and EdU: "When a combination works synergistically, it is like one plus one equals three, instead of something that is additive that is just one plus one equals two," he explained. In other tested tumors, the effect was additive rather than synergistic.
To validate these results further, researchers applied their approach to living tumor samples from patients using UNC’s Screening Live Cancer Explants (SLiCE) Core Facility model. Andrew Satterlee, PhD, assistant professor at UNC Eshelman School of Pharmacy who leads SLiCE Core Facility said: "These experiments demonstrate the power of our SLiCE model to develop and validate new therapies and therapeutic combinations." He added: "We also envision a future where SLiCE can identify the most robust responders to certain therapies to aid therapeutic decision-making in the clinic."
Satterlee suggested that identifying patient sensitivity to specific drug combinations before starting treatment could improve outcomes for glioblastoma patients.
The research team aims to begin human clinical trials seeking FDA approval for this combination therapy. They are also studying treatments tailored to individual patient tumors due to varied responses among different samples.
"We found patient-specific sensitivities to different combination therapies," said Hümeyra Kaanoğlu, co-first author on the study and graduate student in Sancar’s lab. "Such personalized combination therapies in glioblastoma treatment could provide much-needed alternative therapies for this terrible condition."
UNC Health and UNC Lineberger Comprehensive Cancer Center continue offering clinical trials exploring advanced diagnostics and treatments for glioblastoma including CAR-T immunotherapy devices designed to deliver chemotherapies directly into brain tissue.
