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February 11, 2014

Breast Cancer Drug Fights Lethal Fungal Infection in HIV/AIDS Patients

by Jessica Berman

A drug used to treat breast cancer may soon have another use - as a weapon against a lethal fungal infection that kills more HIV/AIDS patients than tuberculosis. The potential new use for tamoxifen was discovered as part of a screening process of older, already approved drugs.
 
Each year, an estimated one million people become infected with Cryptococcus.  Because the fungal infection is particularly deadly to individuals living with AIDS, most cases occur in sub-Saharan Africa, home to 90 percent of individuals with the incurable disease.
 
Cryptococcosis can lead to meningitis, a life-threatening inflammation of the covering of the brain and spinal cord, according to Damian Krysan, a pediatric infectious diseases specialist at the University of Rochester in New York.
 
“It currently kills on the order of three-quarters of a million people a year, primarily again in resource-limited regions with high rates of HIV/AIDS,” says Krysan.
 
Current treatments for the fungal infection are two expensive drugs that are not readily available in developing countries and must be infused through an injection into the blood stream. Under the best of circumstances, experts say 10 to 20 percent of those who receive the treatment die.  
 
Another drug that is used in resource poor countries only slows the growth of the organism, resulting in a higher death rate. 
 
Using an increasingly popular strategy of screening drugs approved for one condition that might be useful against another, researchers led by Krysan sifted through some 2,000 compounds looking for agents that directly kill Cryptococcosis.
 
Investigators hit on tamoxifen, a generic drug that has been used for several decades to treat women with breast cancer.  Krysan says tamoxifen is inexpensive and has a number of important advantages.

“It can be given orally to patients, which is what we needed.  And Cryptococcus causes a brain infection essentially.  And so we needed that drug to get to the brain.  And tamoxifen actually crosses into the central nervous system very effectively and even accumulates to levels above what we see in the blood,” says Krysan.
 
Writing in the journal mBio, Krysan says tamoxifen is most effective against the fungal infection when combined with the drug that is already used to treat Cryptococcus in resource poor countries.
 
More tests are needed.  But because both drugs are already approved, human trials of the combination therapy are not far behind.