Inhibitors of steroidogenesis as agents for the treatment of hormone-dependent cancers

Oestrogens and androgens stimulate growth in hormone-dependent breast and p rostate cancers respectively. Modem strategies seek to remove the influence of hormones on rumour growth using anti-oestrogens (breast) or anti-androg ens (prostate) which block the action of the hormone on its receptor. For p rostate cancer patients LHRH (luteinising hormone releasing hormone), agoni sts, which decrease testes synthesis of testosterone are also used. Newer a lternative (or sequential) strategies aim to deplete circulating and tissue levels of the respective mitogenic hormone by inhibition of a specific tar get enzyme involved in its steroidogenic pathway: for breast cancer - aroma tase (P450(AROM)) or 17 beta -hydroxysteroid dehydrogenase (17 beta -HSD) T ype 1 isoenzyme or the metabolic enzyme oestrogen sulfatase; for prostate c ancer - 17 alpha -hydroxylase: 17, 20-lyase (P450 17) or 5 alpha -steroid r eductase (5 alpha -SR) or 17 beta -HSD Type 3 isoenzyme. The use of P450ARO M inhibitors as sequential agents in breast cancer patients is well establi shed; inhibitors of the other target enzymes are under development and coul d be sequential err combinational agents. Certain P450 17 inhibitors for pr ostatic cancer treatment protect the metabolism of retinoic acid (RAMBAs) a nd 1 alpha ,25-dihydroxy vitamin D-3, thereby being cellular differentiatio n and antiproliferative mimics. These new cytochrome P450 targets and the b uilt-in action of the P450 17 inhibitors may be shown at a later date to al ter or delay the progression of the disease from hormone-dependent to hormo ne-independent. This review discusses the progress made in developing of cl inically useful steroidogenesis inhibitors for the relevant disease and som e of the difficulties encountered in maintaining/achieving remission due to the changing nature of the disease.