Breast Cancer Treatment Tamoxifen Also Fights Deadly Fungal Disease
New findings reveal breast cancer drug Tamoxifen also kills a fungus responsible for deadly brain infection in immunocompromised patients. The findings appear in the online open access journal mBio of the American Society of Microbiology (ASM).
Tamoxifen is intended for the treatment or prevention of breast cancer. AstraZeneca was a primary manufacturer, but discontinued production of Tamoxifen under the brand name Nolvadex in 2006. Generic versions are manufactured and marketed by several other firms including Teva Pharmaceuticals, Mylan Laboratories, and Roxane Laboratories.
Researchers found tamoxifen was an effective antifungal against cryptococcosis, one of the most common human fungal infections. The disease particularly targets immunocompromised patients such as those with HIV/AIDS. The infection manifests as either pneumonia or meningoencephalitis. One-million new Cryptococcosis infections are reported every year, with 620,000 annual deaths worldwide.
Daniel Krysan of the University of Rochester and an author of the study said his group rediscovered tamoxifen when they were screening a large collection of old treatments and drugs against Cryptococcus. “We used clinical microbiology tests to determine whether the molecules had promising activity against Cryptococcus both alone and in combination with other antifungal drugs such as fluconazole. The combination of tamoxifen and fluconazole was synergistic; this means that the combination is more than 4-times more active than either alone.”
They found that tamoxifen worked in a different way when killing the fungus than it does when fighting breast cancer. The drug inhibited proteins connected to a crucial calcium binding protein named calmodulin. Krysan and his colleagues modified the drug to enhance its calmodulin inhibiting ability to improve efficacy against Cryptococcus.
Krysan said their work sets the stage for additional studies to determine whether tamoxifen can be used to design new and better antifungals. “An effective, widely available treatment for cryptococcal meningitis is an unmet clinical need of global importance. These results indicate that tamoxifen is a pharmacologically attractive scaffold for the development of new anti-cryptococcal drugs and provides a mechanistic base for its further optimization,” he said.