Patients with glioblastoma typically live less than 15 months after diagnosis, even after surgery, radiation and chemotherapy. One reason is the blood-brain barrier, which keeps out many of the drugs that might otherwise reach the tumor.
A study in Oncoscience reports a way through it, and the trick is a disguise. The compound is nitrosylcobalamin, or NO-Cbl: vitamin B12, modified so that it releases nitric oxide. Joseph A. Bauer of Nitric Oxide Services, LLC and the Cleveland Clinic Foundation Taussig Cancer Center led the work.
What the animals showed
The technical reality is that this is a rat study, not a human one. The team gave NO-Cbl systemically to rats carrying glioblastoma tumors. The compound crossed the barrier and built up in the tumor tissue.
The detail that matters is how long it stayed. Nitrate levels in the tumor remained elevated for at least 24 hours after treatment, while levels in normal tissue fell away faster. The authors read that as retention: the molecule lingers in the tumor and keeps delivering nitric oxide. Two figures in the paper show sustained nitrate and cobalamin-related metabolites in brain tumor tissue compared with other organs.
The team also ran the compound against cells in the NCI-60 human tumor cell line panel. It showed antitumor activity across many cancer types, with cells from the central nervous system moderately sensitive.
Working alongside existing drugs
In dishes of U87 and D54 glioblastoma cells, NO-Cbl paired with either TRAIL or temozolomide suppressed growth much more strongly than any of them 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 authors wrote.
Earlier research cited in the paper suggests the compound can trigger apoptosis through caspase-8, dampen NF-kB survival signaling and strengthen TRAIL receptor signaling. That might make tumors that have stopped responding to temozolomide more vulnerable again.
The authors call it a pilot translational study and say more research is needed before anyone considers clinical use. Next come validation in a more realistic tumor setting, dose optimization, longer tracking of nitric oxide activity and tests in other central nervous system tumor models.
