La résistance à la castration: mécanismes physiopathologiques et applications thérapeutiques.

Knowledge acquired over the last decade has shown that castration-resistant prostate cancer (CRPC) remains sensitive to treatments that target androgen receptors (AR) and their ligands. Intracrine synthesis of androgens and the increase in AR expression are the main mechanisms involved in CRPC tumour growth. Abiraterone acetate (AA) is a selective inhibitor of the P450 c17 (CYP17) cytochrome, a principal enzyme involved in androgen synthesis. A phase III trial has demonstrated an increased survival rate in patients who have had failed preliminary chemotherapy with docetaxel. Promising results were obtained from a phase II trial with MDV3100, a second-generation anti-androgen, with an increased AR affinity compared with bicalutamide, and that limits its nuclear translocation, its DNA binding and the recruitment of transcription coactivators. Subsequent studies will need to determine the optimum use sequences for these molecules, their potential use in association, and their optimum integration with new emerging treatments. [ABSTRACT FROM AUTHOR]