Could Glioblastoma be Treated by Targeting its Circadian Clock?

Scientists from the University of South California (USC) and UC San Diego have discovered a potential novel circadian “clock” target for treating glioblastoma – a rare and nearly always fatal form of brain cancer. The target controls how the tumor grows, spreads and develops resistance to current treatment therapies. Their findings were recently published in the journal Cancer Discovery.

“We think this is opening the door to a whole new range of therapies,” said Steve Kay, Provost Professor of neurology, biomedical engineering and biological sciences at the Keck School of Medicine of USC in a press release about the study. Prof. Kay conducted the research in collaboration with Jeremy Rich, a neuro-oncologist at University of California, San Diego who specializes in malignant brain tumors. “It’s a great example of collaboration and convergence.”

A Deadly Cancer, A Possible Answer

Glioblastoma is particularly difficult to treat because infiltrates surrounding brain tissue, making it impossible to eliminate, even after surgical intervention coupled with radiation and chemotherapy. The tumor frequently returns due to cancer stem cells left behind. Now, scientists are focusing discerning potential vulnerabilities in those left-behind stem cells by examining the biological clock of glioblastoma in a laboratory setting. According to Prof. Kay, when evaluating the circadian block of glioblastoma cells, the researchers found them “on steroids, on overdrive.” The clock was observed to be ramping up the cells’ metabolism, making the them stronger and more resistant to treatment. Moreover, the cells were able to divide and multiply more rapidly.

Subsequently, the researchers, in collaboration with Synchronicity Pharma, utilized a small-molecule drug to target the proteins in the stem cells’ circadian clocks to disrupt their activity. This caused the accelerated metabolism to subside, and the cells quickly died. “This was a striking, amazing result nobody really predicted,” Prof. Kay said.

Moreover, the researchers tested the small-molecule drug using an animal-model of glioblastoma. The results found the animal models lived longer and the tumor shrank in size.

Prof. Kay added this research “lays the groundwork for us to explore this as a novel therapy for glioblastoma. In the near future, we’re going to do more work with animal models of the tumor and compare our new drug with the current standard of care. Perhaps we can one day contribute towards meeting this terrible unmet medical need.”