Steroidal CYP17 inhibitors for prostate cancer treatment: from concept to clinic

The successful application of therapeutic strategies to block the known growth stimulation property of estrogen in breast cancer, namely the aromatase (CYP19) inhibitors formestane (4-OH) and exemestane (Aromasin) [1], has paved the way for the investigation of inhibitors of other P450 enzymes that might impart the growth of hormone-dependent cancers [2]. Cytochrome P450 17α-hydroxylase,C17,20-lyase (CYP17) is at the crossroads of androgen and corticoid biosynthesis and has become a valuable target in prostate cancer (PC) treatment [3-8]. Androgens, which are produced in steroidogenic tissues, bind to the androgen receptor (AR) and initiate transcription which in turn results in the synthesis of prostate-specific proteins, as well as in cell proliferation. Systemic ablation of androgen by castration, either surgical or chemical, is highly effective in treating PC when the disease is hormone-dependent.