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A new drug combination featuring the widely-known impotence drug Viagra has been found to improve the effectiveness of cancer treatment while protecting the heart from harm caused by a popular form of chemotherapy. With nearly half of all cancer survivors dying from other conditions than cancer, most notably cardiovascular disease, this new treatment is not only innovative but necessary.

Recently presented at the American Heart Association's Scientific Sessions in Los Angeles, the study was co-authored by Rakesh Kukreja, M.S., Ph.D., researcher in the Developmental Therapeutics program at VCU Massey Cancer Center and scientific director at VCU Pauley Heart Center. 

The research team used breast cancer cells and cardiomyocytes (heart cells) to study the effects of combining three drugs. The three drugs included cancer-fighting chemotherapy doxorubicin (Doxil, Andriamycin), erectile dysfunction medication Viagra (sildenafil) and immunosuppressant antibiotic rapamycin (sirolimus, Rapamune).

For decades, doxorubicin has been a powerful and effective drug for patients with various types of cancer, such as breast, ovarian, colon and prostate. Unfortunately, the drug can cause harmful and irreversible side effects to the heart.

Over the past 15 years, researchers have been working to find an optimal therapeutic intervention for protecting the heart against damage caused by doxorubicin.

"Currently, dexrazoxane is the only FDA-approved drug that can prevent heart damage caused by doxorubicin. But, this drug can decrease patients' bone marrow activity, resulting in fewer red blood cells, white blood cells and platelets, and interfere with the anti-cancer efficacy of doxorubicin," explains Kukreja.

In earlier studies, Kukreja and his colleagues found that administering Viagra before doxorubicin prevented heart damage in mice while triggering cell death in prostate cancer cells. He and his research team were also the first to demonstrate in preclinical animal models that rapamycin protects the heart against tissue damage following acute heart attack.

With that in mind, the researchers developed a new 'drug trifecta' that has been found to not only improve the anti-cancer effects of doxorubicin, but to also reduce damage to the heart caused by doxorubicin.

"Because Viagra and rapamycin are clinically approved drugs that both protect heart muscle, we thought that combining these with doxorubicin would be a promising strategy to eliminate the cardiac side effects of the drug while further improving its cancer-killing ability. Such a unique combination has never been used before," said Kukreja.

What they found was that the drug combination led to a dramatic protection of heart cells from apoptosis (naturally occurring programmed cell suicide) and necrosis (cell death caused by infection, toxins or trauma) while significantly improving the anti-cancer effects of doxorubicin .

Researchers say the next step in the study will be to demonstrate how the drug trio improves cancer treatment in animal models with human cancers. Also, more research is needed to understand how Viagra and rapamycin work together to improve doxorubicin treatment.

"Since all of these drugs are clinically approved, we are hopeful that this unique combination therapy may have excellent potential for future clinical trials in cancer patients," Kukreja says.

The full abstract of this study can be found online at: http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=6ba1f3a6-681f-44c5-b6f4-6f4554516b27&cKey=9b5ef827-43cd-4505-a0f3-3faee48f349f&mKey=%7B14145D5B-F96B-4354-8237-8F0937744BA4%7D

Collaborators on this study were David Durrant, Ph.D. candidate at the VCU School of Medicine, Anindita Das, Ph.D., assistant professor at the VCU School of Medicine and researcher at VCU Massey Cancer Center, and Fadi N. Salloum, Ph.D., assistant professor at the VCU Pauley Heart Center.

This research was supported, in part, with funding from the National Institutes of Health grants HL51045, HL79424 and HL93685. 

Written by: Massey Communications Office