CYP17 blockade by abiraterone: further evidence for frequent continued hormone-dependence in castration-resistant prostate cancer.
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.
Ang
J E
JE
The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK.
Olmos
D
D
de Bono
J S
JS
D000736:Androstenes; D000737:Androstenols / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008954:Models, Biological; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy*; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000601:surgery*; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors*; D017211:Treatment Failure
D000736:Androstenes; D000737:Androstenols; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D013254:Steroid 17-alpha-Hydroxylase; C089740:abiraterone