title: Intratumoral steroidogenesis in castration-resistant prostate cancer: a target for therapy.
abstract: Development of castration-resistant prostate cancer (CRPC) in a low androgen environment, arising from androgen deprivation therapy (ADT), is a major problem in patients with advanced prostate cancer (PCa). Several mechanisms have been hypothesized to explain the progression of PCa to CRPC during ADT, one of them is so called persistent intratumoral steroidogenesis. The existence of intratumoral steroidogenesis was hinted based on the residual levels of intraprostatic testosterone (T) and dihydrotestosterone (DHT) after ADT. Accumulating evidence has shown that the intraprostatic androgen levels after ADT are sufficient to induce cancer progression. Several studies now have demonstrated that PCa cells are able to produce T and DHT from different androgen precursors, such as cholesterol and the adrenal androgen, dehydroepiandrosterone (DHEA). Furthermore, up-regulation of genes encoding key steroidogenic enzymes in PCa cells seems to be an indicator for active intratumoral steroidogenesis in CRPC cells. Currently, several drugs are being developed targeting those steroidogenic enzymes, some of which are now in clinical trials or are being used as standard care for CRPC patients. In the future, novel agents that target steroidogenesis may add to the arsenal of drugs for CRPC therapy.
authors.affiliation: Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Inna
authors.initials: I
authors.lastname: Armandari
authors.affiliation: Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands ; Department of Urology, Ciptomangunkusumo Hospital, University of Indonesia Faculty of Medicine, Jakarta, Indonesia.
authors.forename: Agus Rizal
authors.initials: AR
authors.lastname: Hamid
authors.affiliation: Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands ; Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
authors.forename: Gerald
authors.initials: G
authors.lastname: Verhaegh
authors.affiliation: Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands ; Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
authors.forename: Jack
authors.initials: J
authors.lastname: Schalken
keywords: Castration-resistant prostatic neoplasms; Enzyme inhibitors; Molecular targeted therapy; Steroidogenesis