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Drug now used to treat erectile dysfuncton may enhance delivery of herceptin to certain brain tumors
Date:5/7/2010

he erectile dysfunction drugs sildenafil (Viagra) and vardenafil (Levitra), which inhibit the enzyme phosphodiesterase 5 (PDE5), could increase the permeability of the blood-brain tumor barrier and boost the effectiveness of the chemotherapy drug doxorubicin.

"No matter how effective against cancer a chemotherapeutic agent may be, it can have little impact on brain tumors if it cannot cross the blood-brain tumor barrier," he said. "As we find new drugs that are able to target these tumor cells, it is imperative that we develop better ways to enable the medications to reach their targets."

In the current study, the researchers examined whether PDE5 inhibitors might also increase the blood-brain tumor barrier's permeability to Herceptin, a monoclonal antibody used to treat lung and breast tumors that are positive for HER2/neu. Herceptin is a large molecule that does not easily cross the blood-brain tumor barrier, a limitation that severely reduces its effectiveness at treating brain metastases.

The researchers first measured vardenafil's effects on the permeability of the blood-brain tumor barrier. Using a mouse model, the scientists showed that vardenafil led to a two-fold increase in the amount of Herceptin that reached brain metastases of lung and breast cancers. Next, they examined whether this increase in blood-brain barrier permeability improved Herceptin's effectiveness at treating these brain metastases by giving mice vardenafil in tandem with Herceptin. The results showed that the combination of vardenafil plus Herceptin boosted mean survival by 20 percent, compared to Herceptin alone (72+/-18 days versus 59+/-9 days).

Mice whose tumors were not HER2-positive did not experience the same increase in survival that those with HER2-positive tumors did when given vardenafil, indicating that the survival benefit was indeed due to an increase in the amount of Herceptin reaching the tumors, says Ljubimova.

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Contact: Sandy Van
sandy@prpacific.com
808-526-1708
Cedars-Sinai Medical Center
Source:Eurekalert

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