Doctors may need to think about not just how they treat brain cancer, but when they do it.
New research from Washington University in St. Louis suggests that the time of day when a brain tumor is tested or treated could affect how well patients respond to chemotherapy.
The study, led by Professor Erik Herzog and published in the Journal of Neuro-Oncology, focuses on glioblastoma (GBM), one of the most aggressive and hard-to-treat brain cancers in the world. Every year, more than 300,000 people are diagnosed with GBM.
The main treatment is a chemotherapy drug called temozolomide, or TMZ. Unfortunately, this drug doesn’t always work well. One reason is that many tumors produce a special protein called MGMT that repairs the damage TMZ tries to cause. This helps the cancer cells survive, making treatment less effective.
But this new research shows that MGMT levels don’t stay the same throughout the day. Both the gene that controls MGMT and the actual MGMT protein go up and down based on the body’s internal clock, also known as the circadian rhythm.
That led the researchers to wonder: Could the time of day when a biopsy is taken—or when chemotherapy is given—change how the tumor behaves or responds?
To find out, the team looked at five years of brain cancer biopsy data from Washington University medical patients. They found something surprising.
When tumors were tested in the morning, they were more likely to be labeled as “methylated.” Methylation turns off the MGMT gene, meaning the tumor is more likely to respond well to TMZ. In simple terms, morning biopsies may make a tumor look more treatable.
The team believes this timing could change how doctors diagnose and treat brain cancer. It’s a new idea called “chronodiagnostics”—diagnosing based on time of day.
The study also looked at whether giving TMZ at specific times could improve its effectiveness. Graduate student Maria Gonzalez-Aponte measured MGMT protein levels in cancer cells and patient samples at different times of the day. She found that the levels rose and fell in a predictable pattern.
With the help of math biologist Olivia Walch, they built a mathematical model to find the best time to give TMZ. Since TMZ needs several hours to work, the model showed that giving the drug right after MGMT levels peak gives it more time to act while the tumor’s defenses are low.
Walch explained that while the idea of timing medicine sounds simple, the reality is more complex. Everyone’s body clock is a little different, and medicine works differently in different people. But using math can help doctors find the best timing for each person.
This research could lead to better treatment plans not just for TMZ, but for other drugs that work in similar ways. Herzog’s lab is also planning to study other medications used for GBM, such as dexamethasone, which is used to reduce brain swelling. They believe that giving drugs at the wrong time might even help the tumor grow.
In summary, the study shows that paying attention to the time of day could make a real difference in how we treat brain cancer. Morning biopsies might offer more accurate diagnoses, and timing chemotherapy carefully could help drugs work better and give patients a better chance.
The idea of using the body’s clock to guide treatment—called chronotherapy—is growing, and studies like this are showing why it matters.
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The study is published in Journal of Neuro-Oncology.
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