Conclusion

PC is one of the most prevalent causes of death in Europe and USA. In spite of important advances in the treatment of localized disease, advanced PC is still incurable. One of the most relevant PC therapeutic strategies involves the inhibition of androgen biosynthesis by

CYP17 inhibition. In fact, starting from the structure of the natural substrates of this enzyme, several steroids, mainly with a heterocyclic ring bound to C17, have been developed over the years as CYP17 inhibitors. All these studies successfully led to the approval of abiraterone acetate 3 by the FDA in 2011 for the treatment of mCRPC after chemotherapy. In addition, other clinical trials involving this drug are being performed in order to expand its clinical usefulness, namely in CRPC prior to chemotherapy and in combination with other drugs. Another steroid that is in Phase I/II clinical trials for CRPC is galeterone 4, which is structurally similar to abiraterone 21. However, in addition to bearing a potent and selective CYP17 inhibitory activity, this compound also modulates AR activity. As it is now clear that function of the AR axis remains crucial to a majority of patients with CRPC, its mechanism of action can be of great advantage in PC therapy, either alone or in combination with other AR-modulating agents.In the future it is expected that the invaluable knowledge provided by the use of CYP17 inhibitors in PC treatment will shed more light on the most significant biological pathways involved in this disease. The establishment of a possible role for combination regimens including CYP17 inhibitors in earlier stages of PC as a means to prevent surgery and classical chemotherapy drugs would undoubtedly contribute to improving the quality of life of PC patients.

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