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Tamoxifen targets fungal infections: a new use for an old drug?
A new use for the breast cancer drug tamoxifen could bring new hope for HIV/AIDS patients affected by the fungus Cryptococcosis. This fungus causes either pneumonia or the brain infection meningoencephalitis and manifests mainly in HIV/AIDS patients due to their immunosuppressed status. It causes more deaths in this population than, for example, tuberculosis. Overall, it is responsible for approximately 620,000 deaths internationally each year. The study, led by researchers in the laboratory of Dr Damian Krysan in the University of Rochester in the USA, was a response to the fact that therapies for this disease have not substantially advanced since the 1950s and that the gold standard treatment of amphotericin B and 5-flucytosine is not readily available in areas like sub-Saharan Africa where it is most needed. In these areas, fluconazole is standardly used for treatment of Cryptococcosis, being cheaper and more readily available, but unfortunately it is also much less effective.

The current study, to be published in mBio, the online open-access journal of the American Society for Microbiology (ASM.), follows a growing trend of re-examining old drugs to see if they are effective against targets different from their normal uses. Tamoxifen is a breast cancer drug, but in clinical microbiological tests Dr Krysan’s group discovered that it was effective in killing Cryptococcus. Importantly, it acted synergistically with fluconazole; combining the drugs resulted in four-times greater effectiveness than using either alone. The study also showed that tamoxifen uses a different strategy in killing Cryptococcus compared to how it works against breast cancer. It targets calmodulin-related proteins. This offers an important clue as to the types of strategies that may be important developing newer drugs to target Cryptococcus; the researchers found that if tamoxifen was modified to be more effective in interfering with calmodulin, it also became more effective in killing the fungus.

Dr Krysan concluded that: "This work sets the stage for additional animal studies to see if tamoxifen can be used as a drug in people and will allow us to design new drugs related to tamoxifen that are better antifungals".

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