Nitric oxide is a hard thing to aim. A vitamin B12 derivative called nitrosylcobalamin, or NO-Cbl, appears to do it: in animal experiments it slipped across the blood-brain barrier and delivered the gas to glioblastoma tumors.
The paper, in Oncoscience, was led by Joseph A. Bauer of Nitric Oxide Services, LLC and the Cleveland Clinic Foundation Taussig Cancer Center. Its target is a cancer that patients typically survive for less than 15 months, surgery, radiation and chemotherapy included.
The barrier is part of the problem. It blocks many drugs from reaching brain tumors at all.
What the animals showed
After systemic dosing in rats with glioblastoma, NO-Cbl built up preferentially in tumor tissue. Nitrate levels there stayed elevated for at least 24 hours. In normal tissue they dropped off sooner, which the researchers read as a sign the compound is retained in the tumor and releases nitric oxide into its surroundings.
Separately, NO-Cbl was tested on the NCI-60 human tumor cell panel. It was active against a wide range of cancers, and central nervous system cells were moderately sensitive.
The combination work is where the numbers get interesting. In U87 and D54 glioblastoma cells, NO-Cbl plus temozolomide, or plus the experimental agent TRAIL, held tumor growth down much better than any single treatment. The authors report synergy across multiple dose ranges.
Their own summary: “This pilot study demonstrates that NO-Cbl crosses the BBB, accumulates selectively in brain tumor tissue, and synergizes with established and experimental glioblastoma therapies.”
Earlier research cited in the paper links NO-Cbl to caspase-8 activation, suppressed NF-κB survival signaling and stronger TRAIL receptor signaling through S-nitrosylation. Those effects could make cells more responsive to therapy, including tumors that have become resistant to temozolomide.
Not a treatment yet
The authors say plainly that this is pilot translational work and needs further research before clinical use is considered. The to-do list: orthotopic validation, dosing strategies, tracking nitric oxide activity over longer periods, and mechanism studies in more central nervous system tumor models.
