In a study using laboratory animals, researchers found that medications commonly prescribed for erectile dysfunction opened a mechanism called the blood-brain tumor barrier and increased delivery of cancer-fighting drugs to malignant brain tumors.
The experiments were conducted at Cedars-Sinai Medical Center's Maxine Dunitz Neurosurgical Institute and published in Brain Research.
Viagra (sildenafil) and Levitra (vardenafil) are known as PDE5 inhibitors because they block an enzyme, phosphodiesterase5, which interrupts a series of biochemical events that cause the decreased blood flow of erectile dysfunction. This laboratory rat study, published online ahead of print in the journal, found that similar biochemical interactions in the small vessels of the brain play a major role in the blood-brain tumor barrier, which impedes delivery of anti-tumor drugs into brain tumors. PDE5 inhibitors were found to open the barrier and increase drug transport in this early animal study.
Although the normal blood-brain barrier, which regulates access to the brain from the bloodstream, shares many characteristics with the blood-brain tumor barrier, the signaling mechanism blocked by PDE5 inhibitors is unique to the blood-brain tumor barrier. This allows the PDE5 inhibitors to selectively increase drug transport to malignant brain tumors without affecting normal brain tissue.
According to the researchers, these findings may have significant implications in improving drug delivery to brain tumors in patients.
"This is the first study to show that oral administration of PDE5 inhibitors increases the rate of transport of compounds across the blood-brain tumor barrier and improves the effectiveness of the anti-tumor drug adriamycin in the treatment of brain tumors in a rat model. We chose adriamycin for this study because it is one of the most effective drugs against brain tumor cell lines in the laboratory but it has very little effect in animals and humans because it is unable to cross the blood-brain tumor barrier. The combination of vardenafil and adriamycin resulted in longer survival and smaller tumor size," said neurosurgeon Keith L. Black, M.D., chairman of the Department of Neurosurgery at Cedars-Sinai Medical Center and director of the Maxine Dunitz Neurosurgical Institute.