Scientists have discovered that SHP1705, a new compound, shows promising results in suppressing cancer cell growth and survival.
The research, published in Neuro-Oncology, demonstrates that SHP1705 specifically targets circadian clock proteins controlled by glioblastoma stem cells, thereby hindering cancer cell proliferation and viability.
Glioblastoma, the most prevalent malignant brain tumor in adults, is notoriously difficult to treat. Despite combining surgery, radiation therapy, and chemotherapy, tumors often recur and resist treatment.
Recent studies suggest that circadian clock proteins, which regulate sleep-wake cycles and other cellular rhythms, could be crucial in glioblastoma treatment.
Building on previous findings that circadian clock proteins fuel brain cancer stem cell growth, the research team hypothesized that targeting these proteins could effectively curb cancer cell proliferation.
Through a series of preclinical trials, including biochemical, cellular, and animal studies, the team demonstrated that SHP1705 could effectively neutralize glioblastoma stem cells. A Phase 1 clinical trial, conducted by Synchronicity Pharma, a biotech startup co-founded by one of the study’s authors, showed that SHP1705 is well tolerated in humans. The trial, which involved 54 healthy volunteers, revealed only mild side effects such as headaches and nausea, with no significant safety concerns.
SHP1705 functions as a Cryptochrome (CRY) protein activator, suppressing the cellular circadian system. Unlike previously studied CRY activators, SHP1705 targets the CRY2 protein, which is abnormally low in glioblastoma cells. This specificity makes glioblastoma cells exceptionally responsive to SHP1705, as it activates the scarce CRY2 protein.
Consequently, SHP1705 can disrupt the cancer cell’s circadian system while minimally affecting healthy brain cells with normal CRY2 levels.
Multiple preclinical trials showed that SHP1705 effectively inhibits cancer stem cell survival while having minimal impact on healthy cells.
The researchers noted that other compounds targeting circadian clock proteins failed to inhibit glioblastoma stem cells. SHP1705 shows promise in targeting Temozolomide-responsive and resistant glioblastoma stem cells, suggesting potential efficacy even in recurrent cases. Higher doses of SHP1705 delayed tumor growth and extended survival in mice, while also enhancing cancer cell death following radiation therapy.
Combining SHP1705 with SR29065, another circadian clock-targeting compound developed by the team, yielded even more promising results. The upcoming Phase 2 clinical trial will investigate SHP1705’s effectiveness alongside conventional glioblastoma treatments.
The researchers highlight that SHP1705’s oral administration could make it a convenient option for patients undergoing intensive cancer treatments.
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