Antitumor activity with CYP17 blockade indicates that castration-resistant prostate cancer frequently remains hormone driven.

Gerhardt Attard, Alison H M Reid, David Olmos, Johann S de Bono

Index: Cancer Res. 69(12) , 4937-40, (2009)

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Abstract

Abiraterone acetate is a potent, selective, and orally bioavailable small molecule inhibitor of CYP17, an enzyme that catalyzes two key serial reactions (17 alpha hydroxylase and 17,20 lyase) in androgen and estrogen biosynthesis. Clinical trials have confirmed that specific inhibition of CYP17 is safe and results in clinically important antitumor activity in up to 70% of castrate patients with advanced prostate cancer resistant to currently available endocrine therapies. These clinical data indicate that castration-resistant prostate cancer frequently remains hormone dependent and has confirmed that this disease should no longer be described as "hormone resistant or refractory". Biomarker studies, including the analysis of ETS gene fusion status, on patients treated with abiraterone acetate may allow enrichment of patients with a sensitive phenotype in future studies of therapeutics targeting CYP17.