Steroid hormones play a crucial role in the growth of estrogen-sensitive and androgen-sensitive cancers, which constitute about 35% of all cancers in women and 25% of all cancers in men, respectively. Blocking both biosynthesis of active steroids as well as their action on hormonal receptor allowed to develop new therapies. The use of specific and better tolerated therapies than chemotherapy has led to clinical outcomes of interest particularly in the treatment of breast cancer (using an antiestrogen) and prostate cancer (using an antiandrogen). Steroid sulfatase (STS) is a key enzyme involved in the production of estrogens and androgens in humans. This enzyme is an attractive therapeutic target to block the biosynthesis of estrogenic and androgenic hormones. Recently, we obtained a multiple-action inhibitor of STS (1  , Figure 1). In fact, in addition to strongly block in vitro the synthesis of sex hormones (estrone from estrone sulfate; IC50= 3.9 nM), this inhibitor also blocks the estrogen receptor (ER) in the manner of an antiestrogen (in T-47D breast cancer cells) and stimulates in the same time the ER in bone cells (Saos-2 cells). Considering the important role of estrogens in breast cancer and their recently reported potential role in prostate cancer, this new family of tetrahydroisoquinoline derivatives opens the door to an innovative hormonal treatment of these diseases.

Development of a new inhibitor of steroid sulfatase that combine oesteogenic and antiestrogenic properties for treatment of breast and prostate cancers

248th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.