New Experimental Drug Targets Body's Circadian Clock to Combat Glioblastoma

Researchers have identified a promising new compound, SHP1705, that specifically targets the circadian clock proteins exploited by glioblastoma stem cells, offering a novel approach to treating this aggressive brain tumor. Glioblastoma, the most prevalent and deadly adult brain cancer, often recurs after standard treatments like surgery, radiation, and chemotherapy, making prognosis poor. The key to this breakthrough lies in the body's internal circadian clock, which regulates daily biological rhythms, including sleep-wake cycles.

In glioblastoma cells, these clock proteins are hijacked to promote tumor growth and survival. By designing drugs that can reactivate these clock mechanisms, scientists aim to disrupt the cancer cells' ability to proliferate. SHP1705 stands out as a potent and selective activator of CRY2, a cryptochrome protein that influences the circadian clock. Since CRY2 levels are abnormally low in glioblastoma cells, SHP1705 effectively increases its activity, shutting down the mitogenic signals that facilitate tumor growth.

Preclinical studies have demonstrated that SHP1705 impairs glioblastoma stem cell viability with minimal effects on healthy brain cells. It was effective against both chemotherapy-sensitive and resistant cell lines and slowed tumor growth in mouse models, also enhancing the efficacy of radiation therapy. Moreover, combining SHP1705 with another clock-targeting compound, SR29065, yielded synergistic effects, further inhibiting tumor progression.

SHP1705 has progressed beyond laboratory tests, completing a phase 1 clinical trial where it was well tolerated with minor side effects such as headaches and nausea. The promising preclinical results and safety profile pave the way for upcoming phase 2 trials, where the drug will be tested alongside existing treatments like surgery, chemotherapy, and radiation.

This innovative approach addresses a critical challenge in glioblastoma therapy: targeting tumor-initiating cells responsible for recurrence. By focusing on the circadian clock machinery hijacked by cancer cells, scientists hope to develop more effective treatments for glioblastoma, potentially improving outcomes for patients affected by this devastating disease. Further research continues into leveraging the circadian biology to develop targeted therapies against glioblastoma and other cancers.

Source: https://medicalxpress.com/news/2025-05-experimental-compound-circadian-clock-machinery.html