Patients with glioblastoma typically live less than 15 months after diagnosis, even after surgery, radiation and chemotherapy. A study in the journal Oncoscience now reports that a modified form of vitamin B12 got into brain tumors in animals and stayed there.
The compound is nitrosylcobalamin, or NO-Cbl. It releases nitric oxide. Joseph A. Bauer of Nitric Oxide Services, LLC and the Cleveland Clinic Foundation Taussig Cancer Center led the work, which asked whether NO-Cbl could pass the blood-brain barrier, the structure that keeps many drugs out of the brain, and gather in glioblastoma tissue.
It could. In rats with glioblastoma tumors, the compound crossed the barrier after systemic administration and built up preferentially in the tumor. Nitrate levels in tumor tissue stayed high for at least 24 hours. In normal tissue they fell faster.
The team also tested NO-Cbl against the NCI-60 panel of human tumor cell lines. It showed antitumor activity across a wide range of cancer types, with cells from the central nervous system moderately sensitive.
Paired with other drugs
In U87 and D54 glioblastoma cells, adding NO-Cbl to temozolomide, a chemotherapy drug, or to the experimental therapy TRAIL suppressed growth far more than either treatment alone. Further analysis found synergy across several dose ranges.
“This pilot study demonstrates that NO-Cbl crosses the BBB, accumulates selectively in brain tumor tissue, and synergizes with established and experimental glioblastoma therapies,” the researchers wrote.
They point to earlier work showing that NO-Cbl can trigger cell death through caspase-8 activation, dampen NF-κB survival signaling and strengthen TRAIL receptor signaling. That could matter for tumors that have stopped responding to temozolomide.
Early days
The authors describe this as a pilot translational study. More research has to come before anyone considers clinical use. Next steps include validation in orthotopic models, work on dosing, tracking nitric oxide activity over longer periods, and studying the mechanisms in additional central nervous system tumor models.
Consult your doctor for medical advice.
Sources
- New vitamin B12 therapy shows promise against deadly brain cancer
- Vitamin B12 compound shows promise against deadly brain cancer
