Prognostic value of blood mRNA expression signatures in castration-resistant prostate cancer: a prospective, two-stage study.

Background: Biomarkers are urgently needed to dissect the heterogeneity of prostate cancer between patients to improve treatment and accelerate drug development. We analysed blood mRNA expression arrays to identify patients with metastatic castration-resistant prostate cancer with poorer outcome.

Methods: Whole blood was collected into PAXgene tubes from patients with castration-resistant prostate cancer and patients with prostate cancer selected for active surveillance.

Clinical and biochemical consequences of CYP17A1 inhibition with abiraterone given with and without exogenous glucocorticoids in castrate men with advanced prostate cancer.

Context: Abiraterone acetate is a small-molecule cytochrome P450 17A1 (CYP17A1) inhibitor that is active in castration-resistant prostate cancer.

Objective: Our objective was to determine the impact of abiraterone with and without dexamethasone treatment on in vivo steroidogenesis.

Design And Methods: We treated 42 castrate, castration-resistant prostate cancer patients with continuous, daily abiraterone acetate and prospectively collected blood and urine before and during abiraterone treatment and after addition of dexamethasone 0.

Significant and sustained antitumor activity in post-docetaxel, castration-resistant prostate cancer with the CYP17 inhibitor abiraterone acetate.

Purpose: The principal objective of this trial was to evaluate the antitumor activity of abiraterone acetate, an oral, specific, irreversible inhibitor of CYP17 in docetaxel-treated patients with castration-resistant prostate cancer (CRPC).

Patients And Methods: In this multicenter, two-stage, phase II study, abiraterone acetate 1,000 mg was administered once daily continuously. The primary end point was achievement of a prostate-specific antigen (PSA) decline of > or = 50% in at least seven of 35 patients.

Selective inhibition of CYP17 with abiraterone acetate is highly active in the treatment of castration-resistant prostate cancer.

Purpose: It has been postulated that castration-resistant prostate cancer (CRPC) commonly remains hormone dependent. Abiraterone acetate is a potent, selective, and orally available inhibitor of CYP17, the key enzyme in androgen and estrogen biosynthesis.

Patients And Methods: This was a phase I/II study of abiraterone acetate in castrate, chemotherapy-naive CRPC patients (n = 54) with phase II expansion at 1,000 mg (n = 42) using a two-stage design to reject the null hypothesis if more than seven patients had a prostate-specific antigen (PSA) decline of > or = 50% (null hypothesis = 0.

Characterization of ERG, AR and PTEN gene status in circulating tumor cells from patients with castration-resistant prostate cancer.

Hormone-driven expression of the ERG oncogene after fusion with TMPRSS2 occurs in 30% to 70% of therapy-naive prostate cancers. Its relevance in castration-resistant prostate cancer (CRPC) remains controversial as ERG is not expressed in some TMPRSS2-ERG androgen-independent xenograft models. However, unlike these models, CRPC patients have an increasing prostate-specific antigen, indicating active androgen receptor signaling.