Qualitative and quantitative hormonal regulation in castration-resistant prostate cancer

Introduction.-Despite initial sensitivity to androgen deprivation, most metastatic prostate "cancer patients will experience recurrence or progression. This evolution, which occurs while seric testosterone level is low, is called castration resistant prostate cancer (CRPC). Material and methods.-MEDLINE database was requested for French or English articles published until September 2012 responding to the following keywords: "castration resistant", "prostatic neoplasms", "androgens", "testosterone", "regulat*". Here is a summary of relevant data concerning both qualitative and quantitative hormonal regulation. Results.-androgen blood testing is not related to tissue concentrations, as prostate cancer cells exhibit higher hormones levels. Despite its higher biological efficiency, dihydrotestosterone is not the only mediator of androgen-dependent transcription. Androgen synthesis implies many pathways including lot of alternative ones. Steroidogenesis can occur out of the testicles and the adrenals, and maybe in tumor cell or tissue. Major and minor androgens levels, as those of co-repressors and activators inside the tumor cell leads to a smooth androgen activity modulation. Many drugs have the ability to block those different steps. Conclusion.-Castration resistance reflects an androgen activity in tumor cells while major androgen pathway activators are lowered. Alternate pathway include steroids pumps, de novo synthesis by tumor cells or their environment, minor androgens activation by co-factors regulation. Many drugs are known to inhibit those escaping ways. Nowadays they are not efficient enough, because of other minor pathways becoming dominant. Investigations are required but would need new detection techniques of low androgen concentrations in blood as in tissues. (C) 2013 Elsevier Masson SAS. All rights reserved.