Does it matter what time of day you have chemotherapy? If you have glioblastoma, scientists think it might.
Researchers at Texas A&M University say that circadian rhythms may be instrumental to developing new therapies for glioblastoma.
Glioblastoma is the most common malignant brain tumor among adults.
It’s particularly aggressive, hard to treat, and has a poor prognosis.
Circadian rhythms are physical, mental, and behavioral changes that follow a daily pattern. These rhythms influence our sleep-wake cycle, release of hormones, and other body functions.
If you’ve ever been jet lagged, you know how it feels to have your internal body clock disrupted.
Disruptions in circadian rhythms have been linked to poor sleep and a variety of serious health problems.
The researchers found that the timed production of a particular protein linked to tumor growth and spread is disrupted in glioblastoma cells.
If that’s correct, doctors could use a patient’s internal body clock to guide the timing of chemotherapy.
The scientists believe this could be more effective in fighting the cancer without harming nearby healthy tissue.
The study was published in BMC Cancer.
Tackling glioblastoma with timing
Glioblastoma is highly invasive and aggressive.
Previous research showed this may be due to a signaling protein called p38 mitogen-activated protein kinase (MAPK).
Increased activity of p38 MAPK usually means a poorer prognosis.
However, MAPK inhibitors are highly toxic and have too many harsh side effects. That makes them of limited use.
The body’s internal clock regulates p38 MAPK. In glioblastoma cells, that regulation is disturbed.
That’s where chronochemotherapy comes in.
It involves treating cancer at a particular time of day to imitate the regular activity of p38 MAPK.
“We tested to see if inhibition of this cancer-promoting protein in glioblastoma cells would alter their invasive properties,” said Deborah Bell-Pedersen, PhD, in a press release. Bell-Pedersen is a co-corresponding author of the study.
“Indeed, we found that inhibition of p38 MAPK at specific times of the day — times when the activity is low in normal glial cells under control of the circadian clock — significantly reduced glioblastoma cell invasiveness to the level of noninvasive glioma cells,” she explained.
Increased effectiveness and less toxicity could mean a better prognosis.
Bell-Pedersen went on to say that chronotherapeutic strategies have been used for other types of cancer.
“However, circadian biology has not been applied to the development of chronotherapeutic strategies for the treatment of glioblastoma, and clinical outcomes for this common primary brain tumor have shown limited improvement over the past 30 years,” she said.
What it could mean in practice
Dr. Santosh Kesari is a neurologist, neuro-oncologist, and chair of the Department of Translational Neurosciences and Neurotherapeutics at the John Wayne Cancer Institute at Providence Saint John’s Health Center in California.
Kesari told Healthline that when treating glioblastoma, you want to get as much of the tumor out as possible.
“But because it’s so invasive into the normal [part of the] brain, it’s very difficult to treat and completely remove,” he said.
He explained that there are four different subtypes or more, depending on how they’re classified. The subtypes are prognostic, so patients with some types do better than those who have other types.
The research out of Texas A&M, said Kesari, is interesting and exciting.
“In the last few years, there have been more and more publications hinting at the same thing this paper has highlighted. The timing of treatment affects response to chemotherapy or targeted therapy. So, if we had a better knowledge of the rhythms of cancer cells and how proteins are cycling in relation to rhythms, instead of giving chemo during the day, it might be given in the evening or early morning to have a better therapeutic index. That means higher response and lower toxicity, which is what they were trying to highlight,” he said.
But it will take time.
This research was conducted on cell cultures.
“Next, they have to validate in an animal model and confirm that this still holds in an animal system. Then, how that can translate into humans, in terms of timing drugs to use for specific cancers. It could be a couple of years. Or it could take much longer,” said Kesari.
Still, he sees it as a promising way to treat glioblastoma and perhaps other cancers.
“There is literature involving many other types of cancers, and this will help shed light on it. The issue, really, is how big an effect can we get. We’ll only learn that by doing more studies. The efficacy is an unknown,” he said.
Then there’s the practical aspect of timing treatment.
“In a hospital, we could do timed treatment easily. But in an outpatient setting, it may be a little difficult to implement IV chemo treatment outside of normal hours. If it’s a pill, then patients can time a pill at home,” explained Kesari.
There are certain times of day where chemotherapy may be more effective against the cancer. There are also certain times when the body is better able to tolerate treatment.
“We need to find the time the cancer is more sensitive and the body is more resistant to the toxic effects. That’s the ideal time,” said Kesari.
Another circadian approach
In a separate recent study, researchers at the Salk Institute used their understanding of circadian cycles to curb growth of glioblastoma tumors in mice.
They did this by blocking the cells’ access to particular nutrients and starving them. Healthy cells are accustomed to circadian rhythms, so they are not affected.
“Given the importance of the circadian clock in the regulation of many cellular and physiological processes, we hypothesize that targeting the circadian clock with drugs may open the way to novel anticancer strategies,” Gabriele Sulli, PhD, the paper’s first and co-corresponding author, said in a press release.
“This study is very exciting because it sheds light on a new, uncharacterized way to treat cancer with very limited toxicity,” she added.
The study is published in the journal Nature.