Steroid sulphatase (STS), involved in the hydrolysis of
steroid sulphates, plays an important role in the formation of both active oestrogens and
androgens. Since these
steroids significantly impact the proliferation of both oestrogen- and
androgen-dependent
cancers, many research groups over the past 30 years have designed and developed STS inhibitors. One of the main contributors to this field has been Prof. Barry Potter, previously at the University of Bath and now at the University of Oxford. Upon Prof. Potter's imminent retirement, this review takes a look back at the work on STS inhibitors and their contribution to our understanding of sulphate biology and as potential therapeutic agents in
hormone-dependent disease. A number of potent STS inhibitors have now been developed, one of which,
Irosustat (STX64, 667Coumate,
BN83495), remains the only one to have completed phase I/II clinical trials against numerous indications (breast, prostate, endometrial). These studies have provided new insights into the origins of
androgens and oestrogens in women and men. In addition to the therapeutic role of STS inhibition in breast and
prostate cancer, there is now good evidence to suggest they may also provide benefits in patients with colorectal and
ovarian cancer, and in treating
endometriosis. To explore the potential of STS inhibitors further, a number of second- and third-generation inhibitors have been developed, together with single molecules that possess
aromatase-STS inhibitory properties. The further development of potent STS inhibitors will allow their potential therapeutic value to be explored in a variety of
hormone-dependent
cancers and possibly other non-oncological conditions.