Glioblastoma is one of the most aggressive and difficult-to-treat forms of brain cancer. Even after surgery, radiation therapy and chemotherapy, most people survive for less than 15 months after diagnosis.
One of the biggest challenges is that many medicines cannot reach the tumour because they are blocked by the blood-brain barrier, a protective layer that shields the brain from harmful substances but also prevents many cancer drugs from entering.
A new study has reported an encouraging approach that may help overcome this problem. The research was published in the journal Oncoscience and was led by Joseph A. Bauer from Nitric Oxide Services, LLC and the Cleveland Clinic Foundation Taussig Cancer Center.
The team investigated a modified form of vitamin B12 called nitrosylcobalamin, or NO-Cbl, to see whether it could cross the blood-brain barrier and deliver treatment directly to glioblastoma tumours.
Vitamin B12 is an essential nutrient that helps keep nerves and blood cells healthy. In this study, scientists modified vitamin B12 so that it could carry and slowly release nitric oxide, a natural molecule that plays many roles in the body. Previous research has suggested that nitric oxide may help kill cancer cells under certain conditions and make them more sensitive to treatment.
To test the new therapy, the researchers carried out several laboratory and animal experiments. They examined how NO-Cbl affected many different cancer cell types, studied how it travelled through the body in rats with glioblastoma, and tested whether combining it with existing brain cancer treatments produced stronger results.
The study found that NO-Cbl showed anti-cancer activity against several types of tumour cells. Importantly, experiments in rats showed that the compound successfully crossed the blood-brain barrier after it was injected into the body. It also accumulated more heavily inside glioblastoma tissue than in healthy tissues, suggesting that it may selectively target brain tumours.
The researchers discovered that the compound remained active in tumour tissue for at least 24 hours. Levels of nitrate, a marker of nitric oxide release, stayed elevated inside tumours while falling more quickly in normal organs. This finding suggests that the treatment may continue working inside the tumour long after it has left other parts of the body.
The team also investigated whether NO-Cbl could improve current treatments. Laboratory studies using human glioblastoma cells showed that combining NO-Cbl with temozolomide, the standard chemotherapy drug for glioblastoma, or with the experimental treatment TRAIL suppressed tumour growth much more effectively than any treatment alone.
The researchers described these combinations as synergistic, meaning they worked better together than expected.
The paper also discusses possible reasons for these effects. Earlier research suggests that NO-Cbl may encourage cancer cells to undergo programmed cell death, reduce survival signals that protect tumour cells and increase their sensitivity to treatment. These actions could help overcome one of glioblastoma's biggest problems, which is resistance to therapy.
The researchers emphasised that this was an early pilot translational study. Much more work is needed before NO-Cbl can be tested routinely in patients. Future studies will investigate the safest doses, confirm the results in additional brain tumour models and better understand exactly how the treatment works.
This study is exciting because it addresses one of the greatest obstacles in brain cancer treatment, which is getting medicines through the blood-brain barrier. The findings are promising, particularly the selective tumour targeting and improved response when combined with existing therapies.
However, the research has so far been limited to laboratory experiments and animal studies, so it cannot yet show that the treatment is safe or effective in people. Clinical trials will be essential before this approach could become a new treatment option.
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Source: Cleveland Clinic Foundation and Nitric Oxide Services, LLC.
Glioblastoma is one of the most aggressive and difficult-to-treat forms of brain cancer. Even after surgery, radiation therapy and chemotherapy, most people survive for less than 15 months after diagnosis.
One of the biggest challenges is that many medicines cannot reach the tumour because they are blocked by the blood-brain barrier, a protective layer that shields the brain from harmful substances but also prevents many cancer drugs from entering.
A new study has reported an encouraging approach that may help overcome this problem. The research was published in the journal Oncoscience and was led by Joseph A. Bauer from Nitric Oxide Services, LLC and the Cleveland Clinic Foundation Taussig Cancer Center.
The team investigated a modified form of vitamin B12 called nitrosylcobalamin, or NO-Cbl, to see whether it could cross the blood-brain barrier and deliver treatment directly to glioblastoma tumours.
Vitamin B12 is an essential nutrient that helps keep nerves and blood cells healthy. In this study, scientists modified vitamin B12 so that it could carry and slowly release nitric oxide, a natural molecule that plays many roles in the body. Previous research has suggested that nitric oxide may help kill cancer cells under certain conditions and make them more sensitive to treatment.
To test the new therapy, the researchers carried out several laboratory and animal experiments. They examined how NO-Cbl affected many different cancer cell types, studied how it travelled through the body in rats with glioblastoma, and tested whether combining it with existing brain cancer treatments produced stronger results.
The study found that NO-Cbl showed anti-cancer activity against several types of tumour cells. Importantly, experiments in rats showed that the compound successfully crossed the blood-brain barrier after it was injected into the body. It also accumulated more heavily inside glioblastoma tissue than in healthy tissues, suggesting that it may selectively target brain tumours.
The researchers discovered that the compound remained active in tumour tissue for at least 24 hours. Levels of nitrate, a marker of nitric oxide release, stayed elevated inside tumours while falling more quickly in normal organs. This finding suggests that the treatment may continue working inside the tumour long after it has left other parts of the body.
The team also investigated whether NO-Cbl could improve current treatments. Laboratory studies using human glioblastoma cells showed that combining NO-Cbl with temozolomide, the standard chemotherapy drug for glioblastoma, or with the experimental treatment TRAIL suppressed tumour growth much more effectively than any treatment alone.
The researchers described these combinations as synergistic, meaning they worked better together than expected.
The paper also discusses possible reasons for these effects. Earlier research suggests that NO-Cbl may encourage cancer cells to undergo programmed cell death, reduce survival signals that protect tumour cells and increase their sensitivity to treatment. These actions could help overcome one of glioblastoma’s biggest problems, which is resistance to therapy.
The researchers emphasised that this was an early pilot translational study. Much more work is needed before NO-Cbl can be tested routinely in patients. Future studies will investigate the safest doses, confirm the results in additional brain tumour models and better understand exactly how the treatment works.
This study is exciting because it addresses one of the greatest obstacles in brain cancer treatment, which is getting medicines through the blood-brain barrier. The findings are promising, particularly the selective tumour targeting and improved response when combined with existing therapies.
However, the research has so far been limited to laboratory experiments and animal studies, so it cannot yet show that the treatment is safe or effective in people. Clinical trials will be essential before this approach could become a new treatment option.
