1. ¹The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey SM2 5PT, UK
2. ²The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK

Correspondence: Dr JS de Bono, Cancer Research UK Centre for Cancer Therapeutics, The Institute for Cancer Research, The Royal Marsden NHS Foundation Trust, Downs Road Sutton, Surrey SM2 5PT, UK. E-mail: jdebono@icr.ac.uk

Received 15 October 2008; Revised 19 December 2008; Accepted 7 January 2009; Published online 17 February 2009.

Abstract

The limited prognosis of patients with castration-resistant prostate cancer (CRPC) on existing hormonal manipulation therapies calls out for the urgent need for new management strategies. The novel, orally available, small-molecule compound, abiraterone acetate, is undergoing evaluation in early clinical trials and emerging data have shown that the selective, irreversible and continuous inhibition of CYP17 is safe with durable responses in CRPC. Importantly, these efficacy data along with strong preclinical evidence indicate that a significant proportion of CRPC remains dependant on ligand-activated androgen receptor (AR) signalling. Coupled with the use of innovative biological molecular techniques, including the characterisation of circulating tumour cells and ETS gene fusion analyses, we have gained insights into the molecular basis of CRPC. We envision that a better understanding of the mechanisms underlying resistance to abiraterone acetate, as well as the development of validated predictive and intermediate endpoint biomarkers to aid both patient selection and monitor response to treatment, will improve the outcome of CRPC patients.