Patients with glioblastoma typically survive less than 15 months after diagnosis, even with surgery, radiation and chemotherapy. A big part of the reason is the blood-brain barrier, the protective lining that keeps toxins out of the brain and blocks most drugs along with them.
A study in the journal Oncoscience describes a way around it, using vitamin B12 as the carrier. Joseph A. Bauer of Nitric Oxide Services, LLC and the Cleveland Clinic Foundation Taussig Cancer Center led the work as first and corresponding author.
A modified vitamin
The compound is nitrosylcobalamin, or NO-Cbl. It is a form of vitamin B12 altered to release nitric oxide, a molecule known to kill cancer cells. The brain takes up cobalamin through specific transport receptors, and the idea is that the modified molecule rides that system across the barrier. Tumors, with their higher metabolic needs, then take in more of it than healthy tissue does.
The team tested it three ways: against the NCI-60 panel of human tumor cell lines, in pharmacokinetic studies of rats with glioblastoma tumors, and in combination with other treatments on human glioblastoma cell lines. NO-Cbl showed antitumor activity across a wide range of cancer types. Cells from tumors of the central nervous system were moderately sensitive.
What happened in the animals
After systemic administration, NO-Cbl crossed the barrier and collected preferentially in glioblastoma tissue. Nitrate levels in the tumors stayed elevated for at least 24 hours, while levels in normal tissue fell faster. The researchers read that as a sign the compound is retained in tumors and delivers nitric oxide directly to them.
In lab studies with U87 and D54 glioblastoma cells, pairing NO-Cbl with either TRAIL or temozolomide suppressed tumor growth far more than any of the three did alone. Temozolomide is the standard chemotherapy for the disease. Further analysis confirmed synergy across multiple 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 paper states. The authors also pointed to earlier research suggesting NO-Cbl can promote apoptosis, suppress NF-kB survival signaling and strengthen TRAIL receptor signaling, which could make resistant tumors more responsive.
Still far from patients
This is preclinical work in animals and cell lines. The compound has not entered Phase I human safety trials, and no treatment based on it exists. The authors stressed that more research is needed before clinical use. Next steps they listed include orthotopic validation, dosing optimization, tracking nitric oxide activity over longer periods and testing in more central nervous system tumor models.
Glioblastoma kills roughly 14,000 Americans a year, according to the American Cancer Society, and MedicalDaily noted that the standard of care, established in 2005, has changed little since. Standard B12 supplements are not the compound used in the study, and the outlet cautioned against taking them as a cancer treatment.
Sources
- New vitamin B12 therapy shows promise against deadly brain cancer
- Scientists Used Vitamin B12 to Sneak a Cancer-Killer into the Brain, and It Worked on Tumors in Animal Studies
