New Vitamin B12-Based Therapy May Help Fight Deadly Brain Cancer, Study Finds

A modified form of vitamin B12 that releases nitric oxide may offer a new strategy against glioblastoma, one of the deadliest and most treatment-resistant forms of brain cancer. Researchers have found that the experimental compound can cross the blood-brain barrier, selectively accumulate in tumour tissue and boost the effectiveness of existing therapies, according to a newly published study in Oncoscience.

Study Finds Novel Compound Reaches Brain Tumours

The study, titled "Selective blood-brain barrier penetration and tumour targeting of nitrosylcobalamin in glioblastoma: Pharmacokinetics, tissue distribution, and synergistic activity with trail and temozolomide," was led by first and corresponding author Joseph A. Bauer of Nitric Oxide Services, LLC and the Cleveland Clinic Foundation Taussig Cancer Center.

Researchers investigated nitrosylcobalamin (NO-Cbl), a modified vitamin B12 molecule designed to release nitric oxide, to determine whether it could penetrate the blood-brain barrier (BBB) and selectively target glioblastoma tumours.

Glioblastoma multiforme (GBM) remains among the most aggressive brain cancers, with patients typically surviving less than 15 months after diagnosis despite surgery, radiation therapy and chemotherapy. One of the biggest treatment challenges is the blood-brain barrier, which prevents many drugs from effectively reaching tumour tissue.

To assess NO-Cbl's potential, researchers tested the compound against cancer cells in the NCI-60 human tumour cell line panel, conducted pharmacokinetic studies in rats carrying glioblastoma tumours and examined its performance alongside other treatments in human glioblastoma cell lines.

The results showed anti-tumour activity across multiple cancer types, with tumour cells originating in the central nervous system demonstrating moderate sensitivity to the treatment.

Blood-Brain Barrier Penetration Offers Key Advantage

One of the study's most significant findings came from animal experiments, where NO-Cbl successfully crossed the blood-brain barrier following systemic administration and accumulated within glioblastoma tissue.

Researchers observed that nitrate levels in tumour tissue remained elevated for at least 24 hours after treatment, while levels in normal tissues declined more rapidly. The findings suggest that NO-Cbl may be retained within tumours for extended periods, enabling targeted nitric oxide delivery to the tumour microenvironment.

Figures 2 and 3 of the study further indicated sustained levels of nitrate and cobalamin-related metabolites in brain tumour tissue compared with other organs, supporting evidence of selective tumour accumulation.

Combination Therapy Shows Stronger Anti-Tumour Effects

The study also explored whether NO-Cbl could enhance the effectiveness of existing glioblastoma treatments. Laboratory experiments involving U87 and D54 glioblastoma cell lines found that combining NO-Cbl with either TRAIL or temozolomide resulted in significantly greater tumour-growth suppression than any of the therapies achieved individually.

Further analysis revealed synergistic effects across multiple dose ranges. "This pilot study demonstrates that NO-Cbl crosses the BBB, accumulates selectively in brain tumour tissue, and synergises with established and experimental glioblastoma therapies."

According to the researchers, NO-Cbl may also help overcome biological mechanisms that enable glioblastoma to resist treatment. Previous studies cited in the paper suggest the compound can promote apoptosis through caspase-8 activation, suppress NF-kB survival signalling and strengthen TRAIL receptor signalling through S-nitrosylation. These mechanisms could potentially improve tumour responsiveness to therapies, including cases where resistance to temozolomide has developed.

The authors cautioned that the findings are based on an early-stage pilot translational study and require further validation before any clinical application. Future research will focus on optimising dosing strategies, evaluating long-term nitric oxide activity, conducting orthotic validation studies and investigating the treatment's effects in additional central nervous system tumour models.

Nevertheless, the findings provide early evidence that a vitamin B12-based nitric oxide donor may represent a promising new therapeutic approach for glioblastoma by combining blood-brain barrier penetration, selective tumour targeting and enhanced activity alongside existing treatments.

(With inputs from ANI)