What's old is new again
New potential off-label use of tamoxifen

It is common practice for FDA-approved drugs find "new life" through off-label usage. This may be accomplished through the administration of the drug by a different route or using a different dosage but more typically by prescribing the drug for a different indication. Though there are strict guidelines outlined by the FDA before approval for a potential therapeutic, interestingly, off-label use is not regulated and is up to the discretion of physicians. Due to this prescription freedom, upwards of one-fifth of all drugs are prescribed off-label.

Recently, researchers in Brazil have discovered a potential off-label use for the oncology drug tamoxifen. Tamoxifen, currently used for the treatment of estrogen receptor positive (ER+) breast cancer and for cancer prevention in high-risk women, is a selective estrogen receptor modulator (SERM). This compound competes with endogenous estrogens for the estrogen receptor and thus interferes with hormone receptor-induced transcriptional activity. As the primary female sex hormone, estrogen is known to stimulate growth of breast tissue and aid in the stress response. Inhibiting estrogen-mediated function in breast tissue may contribute to the anticancer activity of tamoxifen, though the role that estrogen plays in breast cancer is still controversial. Additionally, tamoxifen already has off-label use for anovulatory and bipolar disorders.

Interestingly, tamoxifen has been demonstrated to inhibit the in vitro growth of the protozoan parasite leishmania, the main cause of leishmaniasis. Parasitic burden was also decreased by tamoxifen treatment of a mouse model of Leishmania amazonensis. The mechanism of action is not well understood and further investigation is warranted in order to rule tamoxifen as a potential treatment for this disease in humans.

Most form of leishmaniasis is transmitted through the bite of a sand fly with the clinical manifestations of infection varying from skin sores to spleen and liver damage. The disease is endemic in 88 countries with the most cases reported in Brazil. The most commonly used treatment for leishmania are antimonial compounds which are thought to disrupt energy production or trypanothione metabolism of the parasite. These compounds are toxic, however, so more tolerable agents (i.e. tamoxifen) would represent a safer strategy for treating leishmaniasis.


References:
Tamoxifen might be effective in the treatment of Leishmania amazonensis
Causes of breast cancer - the estrogen controversy
Genetic diversity of Leishmania amazonensis strains isolated in northern Brazil