Featured Research

from universities, journals, and other organizations

Drug now used to treat erectile dysfuncton may enhance delivery of herceptin to certain brain tumors

Date:
May 10, 2010
Source:
Cedars-Sinai Medical Center
Summary:
New research suggests that a drug currently approved to treat erectile dysfunction may significantly enhance the delivery of the anti-cancer drug herceptin to certain hard-to-treat brain tumors. The research could help doctors improve treatments for lung and breast cancers that have metastasized to the brain.

New research by scientists at Cedars-Sinai's Maxine Dunitz Neurosurgical Institute suggests that a drug currently approved to treat erectile dysfunction may significantly enhance the delivery of the anti-cancer drug Herceptin to certain hard-to-treat brain tumors. The research, published in the journal PLoS ONE, could help doctors improve treatments for lung and breast cancers that have metastasized to the brain.

While cancers that originate in the brain are relatively rare -- approximately 22,000 patients are diagnosed with a primary brain tumor every year -- nearly 10 times that many people develop brain tumors from cancers that began elsewhere in the body. Lung cancer remains the leading cause of cancer death in the U.S., and about 20 percent of lung cancers metastasize to the brain. Breast cancer and melanoma may also spread to the brain, and once this happens, the cancer becomes extremely difficult to treat and the prognosis turns poor.

Even if a cancer is susceptible to drugs, these drugs must penetrate the "blood-brain barrier" if they're to treat cancer that's metastasized to the brain. "Mother Nature created this barrier to protect our brains from dangerous substances, but here we need to get through the barrier to deliver the drugs, and that's a problem," says study author Julia Y. Ljubimova, M.D., Ph.D., a research scientist at the Cedars-Sinai Maxine Dunitz Neurosurgical Institute in Los Angeles.

Keith Black, M.D., chairman of Cedars-Sinai's Department of Neurosurgery and director of the Maxine Dunitz Neurosurgical Institute, is the lead research scientist on this project and senior author of the paper. He has studied the blood-brain barrier for about two decades, and his work in this field received the Jacob Javits award from the National Advisory Neurological Disorders and Stroke Council of the National Institutes of Health in June 2000. Since then, research conducted by his team found that the 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.

"Now that we've demonstrated that big molecules can cross the blood-brain tumor barrier, we're going to continue this strategy with other big molecule drugs, such as nanomedicine drugs" says Ljubimova. "This opens a new world for brain tumor treatments."


Story Source:

The above story is based on materials provided by Cedars-Sinai Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. Hu J, Ljubimova JY, Inoue S, Konda B, Patil R, et al. Phosphodiesterase Type 5 Inhibitors Increase Herceptin Transport and Treatment Efficacy in Mouse Metastatic Brain Tumor Models. PLoS ONE, 2010; 5 (4): e10108 DOI: 10.1371/journal.pone.0010108

Cite This Page:

Cedars-Sinai Medical Center. "Drug now used to treat erectile dysfuncton may enhance delivery of herceptin to certain brain tumors." ScienceDaily. ScienceDaily, 10 May 2010. <www.sciencedaily.com/releases/2010/05/100507175257.htm>.
Cedars-Sinai Medical Center. (2010, May 10). Drug now used to treat erectile dysfuncton may enhance delivery of herceptin to certain brain tumors. ScienceDaily. Retrieved July 29, 2014 from www.sciencedaily.com/releases/2010/05/100507175257.htm
Cedars-Sinai Medical Center. "Drug now used to treat erectile dysfuncton may enhance delivery of herceptin to certain brain tumors." ScienceDaily. www.sciencedaily.com/releases/2010/05/100507175257.htm (accessed July 29, 2014).

Share This




More Health & Medicine News

Tuesday, July 29, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Deadly Ebola Virus Threatens West Africa

Deadly Ebola Virus Threatens West Africa

AP (July 28, 2014) West African nations and international health organizations are working to contain the largest Ebola outbreak in history. It's one of the deadliest diseases known to man, but the CDC says it's unlikely to spread in the U.S. (July 28) Video provided by AP
Powered by NewsLook.com
$15B Deal on Vets' Health Care Reached

$15B Deal on Vets' Health Care Reached

AP (July 28, 2014) A bipartisan deal to improve veterans health care would authorize at least $15 billion in emergency spending to fix a veterans program scandalized by long patient wait times and falsified records. (July 28) Video provided by AP
Powered by NewsLook.com
Two Americans Contract Ebola in Liberia

Two Americans Contract Ebola in Liberia

Reuters - US Online Video (July 28, 2014) Two American aid workers in Liberia test positive for Ebola while working to combat the deadliest outbreak of the virus ever. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Traditional African Dishes Teach Healthy Eating

Traditional African Dishes Teach Healthy Eating

AP (July 28, 2014) Classes are being offered nationwide to encourage African Americans to learn about cooking fresh foods based on traditional African cuisine. The program is trying to combat obesity, heart disease and other ailments often linked to diet. (July 28) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins